pharmacokinetics

Summary

Summary: Dynamic and kinetic mechanisms of exogenous chemical and drug ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and TOXICOLOGY as a function of dosage, and rate of METABOLISM. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. ADME and ADMET are short-hand abbreviations for absorption, distribution, metabolism, elimination and toxicology.

Top Publications

  1. ncbi When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly
    Klaus Turnheim
    Institut fur Pharmakologie, Universitat Wien, Währinger Str 13a, Vienna A 1090, Austria
    Exp Gerontol 38:843-53. 2003
  2. ncbi Population pharmacokinetics III: design, analysis, and application of population pharmacokinetic Studies
    Ene I Ette
    Vertex Pharmaceuticals, Inc, 130 Waverly St, Cambridge, MA 02139 4242, USA
    Ann Pharmacother 38:2136-44. 2004
  3. ncbi Prediction of drug clearance in children: impact of allometric exponents, body weight, and age
    Iftekhar Mahmood
    From the Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
    Ther Drug Monit 29:271-8. 2007
  4. ncbi Pharmacokinetics and biodistribution of nanoparticles
    Shyh Dar Li
    School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Pharm 5:496-504. 2008
  5. pmc Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications
    A A Mangoni
    Department of Health Care of the Elderly, Guy s, King s, and St Thomas School of Medicine, King s College London, London
    Br J Clin Pharmacol 57:6-14. 2004
  6. ncbi Role of P-glycoprotein in pharmacokinetics: clinical implications
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Clin Pharmacokinet 42:59-98. 2003
  7. ncbi Pharmacokinetics of subcutaneous immunoglobulin and their use in dosing of replacement therapy in patients with primary immunodeficiencies
    Melvin Berger
    Immunology Research and Development, CSL Behring, King of Prussia, PA 19406 0901, USA
    Clin Immunol 139:133-41. 2011
  8. ncbi Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach
    Gail D Anderson
    Department of Pharmacy, University of Washington, Seattle, Washington 98195, USA
    Clin Pharmacokinet 44:989-1008. 2005
  9. ncbi Physiologically based pharmacokinetics joined with in vitro-in vivo extrapolation of ADME: a marriage under the arch of systems pharmacology
    A Rostami-Hodjegan
    Centre for Applied Pharmacokinetics Research, School of Pharmacy and Pharmaceutical Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
    Clin Pharmacol Ther 92:50-61. 2012
  10. ncbi A comparison of pharmacokinetics between humans and monkeys
    Takafumi Akabane
    Analysis and Pharmacokinetics Research Laboratories, Discovery Drug Metabolism and Pharmacokinetics, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba City, Ibaraki 305 8585, Japan
    Drug Metab Dispos 38:308-16. 2010

Detail Information

Publications275 found, 100 shown here

  1. ncbi When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly
    Klaus Turnheim
    Institut fur Pharmakologie, Universitat Wien, Währinger Str 13a, Vienna A 1090, Austria
    Exp Gerontol 38:843-53. 2003
    ..Hence drugs should be used very restrictively in geriatric patients. If drug therapy is absolutely necessary, the dosage should be titrated to a clearly defined clinical or biochemical therapeutic goal starting from a low initial dose...
  2. ncbi Population pharmacokinetics III: design, analysis, and application of population pharmacokinetic Studies
    Ene I Ette
    Vertex Pharmaceuticals, Inc, 130 Waverly St, Cambridge, MA 02139 4242, USA
    Ann Pharmacother 38:2136-44. 2004
    ..To present a framework within which population pharmacokinetic (PPK) studies should be designed and analyzed and discuss the application of developed PPK models...
  3. ncbi Prediction of drug clearance in children: impact of allometric exponents, body weight, and age
    Iftekhar Mahmood
    From the Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
    Ther Drug Monit 29:271-8. 2007
    ..75 should be replaced by the exponent of the allometric equation developed for that drug...
  4. ncbi Pharmacokinetics and biodistribution of nanoparticles
    Shyh Dar Li
    School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Pharm 5:496-504. 2008
    ..The pharmacokinetics (PK) and tissue distribution of the nanoparticles largely define their therapeutic effect and toxicity...
  5. pmc Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications
    A A Mangoni
    Department of Health Care of the Elderly, Guy s, King s, and St Thomas School of Medicine, King s College London, London
    Br J Clin Pharmacol 57:6-14. 2004
    ..This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.
  6. ncbi Role of P-glycoprotein in pharmacokinetics: clinical implications
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Clin Pharmacokinet 42:59-98. 2003
    ..Because of its importance in pharmacokinetics, P-glycoprotein transport screening has been incorporated into the drug discovery process, aided by the ..
  7. ncbi Pharmacokinetics of subcutaneous immunoglobulin and their use in dosing of replacement therapy in patients with primary immunodeficiencies
    Melvin Berger
    Immunology Research and Development, CSL Behring, King of Prussia, PA 19406 0901, USA
    Clin Immunol 139:133-41. 2011
    Bioavailability and pharmacokinetics of subcutaneous IgG (SCIG) and intravenous IgG (IVIG) differ. It is not clear if and/or how the dose should be adjusted when switching from IVIG to SCIG...
  8. ncbi Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach
    Gail D Anderson
    Department of Pharmacy, University of Washington, Seattle, Washington 98195, USA
    Clin Pharmacokinet 44:989-1008. 2005
    ..This same method can also be used to improve our understanding regarding the effect of pregnancy on pharmacokinetics of drugs. Limited studies suggest bioavailability of drugs is not altered during pregnancy...
  9. ncbi Physiologically based pharmacokinetics joined with in vitro-in vivo extrapolation of ADME: a marriage under the arch of systems pharmacology
    A Rostami-Hodjegan
    Centre for Applied Pharmacokinetics Research, School of Pharmacy and Pharmaceutical Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
    Clin Pharmacol Ther 92:50-61. 2012
    Classic pharmacokinetics (PK) rarely takes into account the full knowledge of physiology and biology of the human body. However, physiologically based PK (PBPK) is built mainly from drug-independent "system" information...
  10. ncbi A comparison of pharmacokinetics between humans and monkeys
    Takafumi Akabane
    Analysis and Pharmacokinetics Research Laboratories, Discovery Drug Metabolism and Pharmacokinetics, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba City, Ibaraki 305 8585, Japan
    Drug Metab Dispos 38:308-16. 2010
    ..humans, and that bioavailability in cynomolgus monkeys after oral administration is unsuitable for predicting pharmacokinetics in humans...
  11. ncbi Mechanism-based concepts of size and maturity in pharmacokinetics
    B J Anderson
    Department of Anaesthesiology, University of Auckland School of Medicine, Auckland, New Zealand
    Annu Rev Pharmacol Toxicol 48:303-32. 2008
    ..A sigmoid E(max) model (Hill equation) describes gradual maturation of clearance in early life leading to a mature adult clearance achieved at a later age...
  12. pmc Impact of OATP transporters on pharmacokinetics
    A Kalliokoski
    Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland
    Br J Pharmacol 158:693-705. 2009
    ..polypeptides (OATP) form a family of influx transporters expressed in various tissues important for pharmacokinetics. Of the 11 human OATP transporters, OATP1B1, OATP1B3 and OATP2B1 are expressed on the sinusoidal membrane of ..
  13. ncbi Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties
    S M Moghimi
    Molecular Targeting and Polymer Toxicology Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, BN2 4GJ, Brighton, UK
    Prog Lipid Res 42:463-78. 2003
    ..For example, stimulated or newly recruited macrophages can recognize and rapidly internalize sterically protected nanoparticles by opsonic-independent mechanisms. These concepts are also examined...
  14. ncbi ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions
    Béatrice Marquez
    Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Universite Catholique de Louvain, B 1200 Brussels, Belgium
    Curr Drug Targets 12:600-20. 2011
    ..All together, these data justify why studying drug active transport should be part of the evaluation of new drugs, as recently recommended by the FDA...
  15. ncbi An integrated metabolomics and pharmacokinetics strategy for multi-component drugs evaluation
    Ke Lan
    Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan 610041, PR China
    Curr Drug Metab 11:105-14. 2010
    ..The pharmacokinetics (PK) of multi-component therapeutics is a great technical challenge, which has led to significant limitations ..
  16. ncbi Population pharmacokinetics I: background, concepts, and models
    Ene I Ette
    Vertex Pharmaceuticals, Inc, Cambridge, MA, USA
    Ann Pharmacother 38:1702-6. 2004
    ....
  17. ncbi Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles
    Donald E Owens
    Department of Chemical Engineering, University of Texas at Austin, 1 University Station, C0400, Austin, TX 78712, USA
    Int J Pharm 307:93-102. 2006
    ..This method creates a hydrophilic protective layer around the nanoparticles that is able to repel the absorption of opsonin proteins via steric repulsion forces, thereby blocking and delaying the first step in the opsonization process...
  18. ncbi Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds
    R Scott Obach
    Pharmacokinetics Dynamics and Metabolism, Pfizer Global Research and Development, Groton Laboratories, Groton, Connecticut, USA
    Drug Metab Dispos 36:1385-405. 2008
    ....
  19. ncbi Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs
    Bradley L Urquhart
    Division of Clinical Pharmacology, London Health Sciences Centre University Hospital, Room ALL 152, 339 Windermere Road, London, Ontario N6A 5A5, Canada
    J Clin Pharmacol 47:566-78. 2007
    ..Finally, they outline how the drug development process has been affected by the current understanding of the involvement of nuclear receptors in the regulation of drug disposition genes...
  20. ncbi Relative impact of incorporating pharmacokinetics on predicting in vivo hazard and mode of action from high-throughput in vitro toxicity assays
    Barbara A Wetmore
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 132:327-46. 2013
    ..Adjusting the in vitro assays for pharmacokinetics did not improve the ability to predict in vivo effects as either a discrete (yes or no) response or a low ..
  21. ncbi Advances in paediatric pharmacokinetics
    Catherijne A J Knibbe
    University of Leiden, Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden, The Netherlands
    Expert Opin Drug Metab Toxicol 7:1-8. 2011
    In recent years, interest in paediatric pharmacokinetics has grown...
  22. ncbi Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole
    Jenny Y Chien
    Department of Drug Disposition, Lilly Research Laboratories, Indianapolis, IN 46285, USA
    Drug Metab Dispos 34:1208-19. 2006
    ..The model may be used prospectively to improve the quantitative prediction of CYP3A inhibition and aid the optimization of study designs for CYP3A-mediated drug-drug interaction studies in drug development...
  23. ncbi Population pharmacokinetics II: estimation methods
    Ene I Ette
    Vertex Pharmaceuticals, Inc, Cambridge, MA, USA
    Ann Pharmacother 38:1907-15. 2004
    ....
  24. pmc The role of transporters in the pharmacokinetics of orally administered drugs
    Sarah Shugarts
    Department of Biopharmaceutical Sciences, University of California, San Francisco, CA 94143 0912, USA
    Pharm Res 26:2039-54. 2009
    ....
  25. ncbi Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective
    S M Moghimi
    Centre for Pharmaceutical Nanotechnology and Nanotoxicology, University of Copenhagen, DK 2100 Copenhagen Ø, Denmark
    Annu Rev Pharmacol Toxicol 52:481-503. 2012
    ..b>Pharmacokinetics and biodistribution of these carriers are controlled by a complex array of interrelated core and interfacial ..
  26. ncbi Update on the pharmacokinetics and redox properties of protein-bound uremic toxins
    Hiroshi Watanabe
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862 0973, Japan
    J Pharm Sci 100:3682-95. 2011
    ..In this review, we summarized the recent works providing the new insight on the pharmacokinetics and redox properties of these uremic toxins...
  27. pmc INDI: a computational framework for inferring drug interactions and their associated recommendations
    Assaf Gottlieb
    The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
    Mol Syst Biol 8:592. 2012
    ..Most computational inference methods focus on modeling drug pharmacokinetics, aiming at interactions that result from a common metabolizing enzyme (CYP)...
  28. ncbi CSF as a surrogate for assessing CNS exposure: an industrial perspective
    Jiunn H Lin
    Department of Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Curr Drug Metab 9:46-59. 2008
    ..Depending on the physicochemical properties of drugs and the site/timing of CSF sampling, the unbound drug concentration at the biophase within the brain could differ significantly from the corresponding CSF drug concentration...
  29. ncbi Sulfur mustard toxicity: history, chemistry, pharmacokinetics, and pharmacodynamics
    Kamyar Ghabili
    Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
    Crit Rev Toxicol 41:384-403. 2011
    ..in 1917, SM and other mustard agents have been the subjects of intensive research, and their chemistry, pharmacokinetics and mechanisms of toxic action are now fairly well understood...
  30. ncbi Preclinical prediction of human brain target site concentrations: considerations in extrapolating to the clinical setting
    Joost Westerhout
    Department of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands
    J Pharm Sci 100:3577-93. 2011
    ..g., inhibition of an efflux transporter or induction of pathological state). With the use of advanced mathematical modeling procedures, we may dissect contributions of individual mechanisms in animals as links to the human situation...
  31. ncbi PK/PD modelling and beyond: impact on drug development
    Douwe D Breimer
    Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
    Pharm Res 25:2720-2. 2008
    ..This will give rise to new opportunities of drug combinations, which can only be developed rationally through the appropriate application of dynamical systems-based PK/PD models...
  32. ncbi The dynamics of drug action on the within-host population growth of infectious agents: melding pharmacokinetics with pathogen population dynamics
    D J Austin
    Wellcome Trust Centre for the Epidemiology of Infectious Diseases, University of Oxford, South Parks Road, Oxford, OX1 3PS, U K
    J Theor Biol 194:313-39. 1998
    ..Under chemotherapeutic regimens, expressions for R0 are derived allowing estimates to be made of the ideal treatment regime required to eliminate the pathogen, both for HIV and P. falciparum malaria...
  33. ncbi Sex differences in pharmacokinetics and pharmacodynamics
    Monica Gandhi
    Division of Infectious Diseases, Department of Medicine, University of California San Francisco, San Francisco, California 94143 1352, USA
    Annu Rev Pharmacol Toxicol 44:499-523. 2004
    ..This review examines the biologic basis of differences in pharmacokinetics and pharmacodynamics between the sexes and summarizes studies that have addressed these differences...
  34. ncbi Pegylation: a novel process for modifying pharmacokinetics
    J M Harris
    Shearwater Corporation, Huntsville, Alabama 35801, USA
    Clin Pharmacokinet 40:539-51. 2001
    ..Because the size, geometry and attachment site of the PEG moiety play a crucial role in determining these properties, therapeutically optimised agents must be designed on a protein-by-protein basis...
  35. ncbi Challenges and obstacles of ocular pharmacokinetics and drug delivery
    Arto Urtti
    Drug Discovery and Development Technology Center, University of Helsinki, Viikinkaari 5 E, 00014 University of Helsinki, Finland
    Adv Drug Deliv Rev 58:1131-5. 2006
    ..Ocular drug delivery is hampered by the barriers protecting the eye. This review presents an overview of the essential factors in ocular pharmacokinetics and selected pharmacological future challenges in ophthalmology.
  36. ncbi Development and evaluation of a generic physiologically based pharmacokinetic model for children
    Andrea N Edginton
    Competence Center Systems Biology, Bayer Technology Services GmbH, Leverkusen, Germany
    Clin Pharmacokinet 45:1013-34. 2006
    ....
  37. ncbi What do we (need to) know about the kinetic properties of nanoparticles in the body?
    Werner I Hagens
    Centre for Substances and Integrated Risk Assessment SIR, National Institute for Public Health and the Environment RIVM, Antonie van Leeuwenhoeklaan 9, P O Box 1, 3720 BA Bilthoven, The Netherlands
    Regul Toxicol Pharmacol 49:217-29. 2007
    ..g. blood and organs). In this paper, the current knowledge on the kinetic properties of nanoparticles is reviewed. Moreover, knowledge gaps from a kinetic point of view (detection, dose, ADME processes) are identified...
  38. ncbi Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development
    Daryl C Drummond
    Hermes Biosciences, Inc, South San Francisco, California 94080, USA
    J Pharm Sci 97:4696-740. 2008
    ..is a function not only of the properties of the encapsulated drug, but to a significant extent of the pharmacokinetics, biodistribution, and drug release rates of the individual carrier...
  39. ncbi Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects
    Charles la Porte
    Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada
    Clin Pharmacokinet 49:449-54. 2010
    ..The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages...
  40. ncbi The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox)
    Gergely Szakacs
    National Medical Center, Institute of Haematology and Immunology, Membrane Research Group of the Hungarian Academy of Sciences, H 1113 Budapest, Diószegi u 64, Hungary
    Drug Discov Today 13:379-93. 2008
    ..The use of the in vitro, in vivo, in silico models, their combination, and the emerging clinical information are evaluated with respect to their potential application in early drug screening...
  41. pmc Predicting drug-drug interactions: an FDA perspective
    Lei Zhang
    Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Rm 3188, Bldg 51, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA
    AAPS J 11:300-6. 2009
    ..This report summarizes critical elements in the in vitro evaluation of drug interaction potential during drug development and uses a case study to highlight the impact of in vitro information on drug labeling...
  42. ncbi Pharmacokinetics and dosage adjustment in patients with renal dysfunction
    Roger K Verbeeck
    Faculty of Pharmacy, Rhodes University, Grahamstown, Eastern Cape, South Africa
    Eur J Clin Pharmacol 65:757-73. 2009
    ..In patients with end-stage renal disease, dialysis techniques such as hemodialysis and continuous ambulatory peritoneal dialysis may remove drugs from the body, necessitating dosage adjustment...
  43. pmc Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption
    Joseph M Custodio
    Department of Biopharmaceutical Sciences, University of California, San Francisco, San Francisco, California 94143 0446, USA
    Adv Drug Deliv Rev 60:717-33. 2008
    ..That is, high fat meals and lipidic excipients would be expected to have little effect on F for Class 1 drugs; they would increase F of Class 2 drugs, while decreasing F for Class 3 drugs...
  44. ncbi Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions
    Trudy Rodgers
    Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, England
    J Pharm Sci 95:1238-57. 2006
    ..Such advancements in parameter prediction will assist WBPBPK modelling, where time, cost and labour requirements greatly deter its application...
  45. ncbi Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates
    Marcia L Buck
    Children s Medical Center and Schools of Medicine and Nursing, University of Virginia Health System, Charlottesville, Virginia 22908, USA
    Clin Pharmacokinet 42:403-17. 2003
    ....
  46. ncbi Preclinical pharmacokinetics: an approach towards safer and efficacious drugs
    Sonu Sundd Singh
    Nektar Therapeutics Private Limited, 1st Floor, 31 A, SD Road, Secunderabad, AP, India
    Curr Drug Metab 7:165-82. 2006
    Lack of efficacy and toxicity are considered to be major reasons for drug failures and pharmacokinetics governs them to a large extent. Compound with favorable pharmacokinetics is more likely to be efficacious and safe...
  47. ncbi Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction
    Roger K Verbeeck
    School of Pharmacy, Catholic University of Louvain, Brussels, Belgium
    Eur J Clin Pharmacol 64:1147-61. 2008
    The liver plays a central role in the pharmacokinetics of the majority of drugs...
  48. pmc Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development
    Jaime A Yáñez
    Department of Drug Metabolism and Pharmacokinetics, Alcon Research Ltd, Fort Worth, TX 76134, USA
    Ther Deliv 2:643-72. 2011
    Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies...
  49. ncbi Population clinical pharmacology of children: general principles
    Brian J Anderson
    Department of Anaesthesiology, University of Auckland, Auckland, New Zealand
    Eur J Pediatr 165:741-6. 2006
    ..Population modelling using mixed-effects models provides a means to study variability in drug responses among individuals representative of those for whom the drug will be used clinically...
  50. ncbi Pharmacokinetics of alemtuzumab and the relevance in clinical practice
    Thomas Elter
    Department of Internal Medicine, University of Cologne, Cologne, Germany
    Leuk Lymphoma 49:2256-62. 2008
    ..The pharmacokinetics (PK) of alemtuzumab is best described by a two-compartment model with large interpatient variability in all ..
  51. ncbi Integrated pharmacokinetics and pharmacodynamics in drug development
    Jasper Dingemanse
    Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland
    Clin Pharmacokinet 46:713-37. 2007
    ..b>Pharmacokinetics and pharmacodynamics are the two main principles determining the relationship between dose and response...
  52. ncbi Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations
    S P Myrand
    Drug Safety Research and Development, Pfizer Global Research and Development PGRD, Ann Arbor, Michigan, USA
    Clin Pharmacol Ther 84:347-61. 2008
    ..We conclude that equivalent plasma drug concentrations and metabolic profiles can be expected for native Japanese, first- and third-generation Japanese, Koreans, and Chinese for compounds handled through these six CYP enzymes...
  53. ncbi The pharmacokinetics of idraparinux, a long-acting indirect factor Xa inhibitor: population pharmacokinetic analysis from Phase III clinical trials
    C Veyrat-Follet
    Sanofi Aventis, Global Metabolism and Pharmacokinetics, Vitry sur Seine, Cedex, France
    J Thromb Haemost 7:559-65. 2009
    ..Idraparinux, a long-acting synthetic pentasaccharide, is a specific antithrombin-dependent inhibitor of activated factor X that has been investigated in the treatment and prevention of thromboembolic events...
  54. ncbi Dried blood spots as a sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of a quantitative bioanalytical method
    Neil Spooner
    PreClinical Development Drug Metabolism and Pharmacokinetics, GlaxoSmithKline Research and Development, Ware, Hertfordshire SG12 0DP, UK
    Anal Chem 81:1557-63. 2009
    ..The validated DBS approach was successfully applied to a clinical study (single oral dose of 500 mg or 1 g acetaminophen)...
  55. ncbi Non-linear mixed-effects models with stochastic differential equations: implementation of an estimation algorithm
    Rune V Overgaard
    Informatics and Mathematical Modelling, Technical University of Denmark, Lyngby, Denmark
    J Pharmacokinet Pharmacodyn 32:85-107. 2005
    ..Fundamental issues concerning the proposed model and estimation algorithm are addressed by simulation studies, concluding that system noise can successfully be separated from measurement noise and inter-individual variability...
  56. ncbi Modulation of pharmacokinetics of radioiodinated sugar-conjugated somatostatin analogues by variation of peptide net charge and carbohydration chemistry
    Margret Schottelius
    Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, 81675 Munchen, Germany
    Bioconjug Chem 16:429-37. 2005
    Sugar conjugation of biooactive peptides has been shown to be a powerful tool to modulate peptide pharmacokinetics. In the case of radiolabeled somatostatin analogues developed for in vivo scintigraphy of somatostatin receptor (sst) ..
  57. ncbi Development of a physiology-based whole-body population model for assessing the influence of individual variability on the pharmacokinetics of drugs
    Stefan Willmann
    Bayer Technology Services GmbH, Process Technology Systems Biology, Building E41, D 51368 Leverkusen, Germany
    J Pharmacokinet Pharmacodyn 34:401-31. 2007
    ..the new population model is well suited to assess the influence of individual physiological variability on the pharmacokinetics of drugs. It is expected that this new tool can be beneficially applied in the planning of clinical studies.
  58. ncbi MDR1 genotype-related pharmacokinetics: fact or fiction?
    Toshiyuki Sakaeda
    Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan
    Drug Metab Pharmacokinet 20:391-414. 2005
    ..for MDR1, and MDR1 and other transporters are recognized as an important class of proteins for regulating pharmacokinetics. The first investigation of the effects of MDR1 genotypes on pharmacotherapy was reported in 2000; a silent ..
  59. ncbi Population clinical pharmacology of children: modelling covariate effects
    Brian J Anderson
    Department of Anaesthesiology, University of Auckland, Auckland, New Zealand
    Eur J Pediatr 165:819-29. 2006
    ..Population modelling using mixed effects models provides a means to study variability in paediatric drug responses among individuals representative of those in whom the drug will be used clinically...
  60. ncbi Drug metabolism and pharmacokinetics in support of drug design
    Wei Tang
    Department of Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, Rahway, NJ, USA
    Curr Pharm Des 15:2170-83. 2009
    b>Pharmacokinetics has been recognized as one of the elements determining the probability of success in pharmaceutical research...
  61. ncbi Age-related changes in pharmacokinetics
    Shaojun Shi
    Department of Pharmacy of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, People s Republic of China
    Curr Drug Metab 12:601-10. 2011
    ..In conclusion, the complexity of interactions between comorbidity, polypharmacy, and age-related changes in pharmacokinetics (and pharmacodynamics) justify the old and well-known dosing aphorism " start low, go slow" for aged ..
  62. ncbi Improvement of pharmacokinetics of radioiodinated Tyr(3)-octreotide by conjugation with carbohydrates
    Margret Schottelius
    Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, 81675 Munchen, Germany
    Bioconjug Chem 13:1021-30. 2002
    ..To overcome the unfavorable pharmacokinetics of radiohalogenated octreotide analogues, we evaluated three carbohydrated conjugates of Tyr(3)-octreotide (..
  63. ncbi Pharmacokinetics and bioavailability of the bioflavonoid biochanin A: effects of quercetin and EGCG on biochanin A disposition in rats
    Young Jin Moon
    Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, New York 14260, USA
    Mol Pharm 4:865-72. 2007
    ..Our findings demonstrate for the first time that the administration of multiple flavonoids results in increased flavonoid bioavailability, as well as a decrease in clearance, potentially due to increased enterohepatic cycling...
  64. ncbi Drug distribution. The forgotten relative in clinical pharmacokinetics
    H G Eichler
    Department of Clinical Pharmacology, University of Vienna, Austria
    Clin Pharmacokinet 34:95-9. 1998
    ..Clinical pharmacology should seek an improved understanding of the biological determinants governing not only plasma but tissue drug concentrations...
  65. ncbi Drug disposition in three dimensions: an update on stereoselectivity in pharmacokinetics
    Dion R Brocks
    Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
    Biopharm Drug Dispos 27:387-406. 2006
    ..Because of enantioselectivity in pharmacokinetics, results of in vitro pharmacodynamic studies involving enantiomers may differ from those in vivo where ..
  66. ncbi Introduction to drug pharmacokinetics in the critically ill patient
    Brian S Smith
    UMass Memorial Medical Center, Worcester, MA 01655, USA
    Chest 141:1327-36. 2012
    ..of drugs for critically ill patients, overall data are limited regarding the impact of critical illness on pharmacokinetics (PK)...
  67. pmc Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications
    P Kannan
    Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
    Clin Pharmacol Ther 86:368-77. 2009
    P-glycoprotein (P-gp), an efflux transporter, controls the pharmacokinetics of various compounds under physiological conditions...
  68. ncbi Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV-C, 10% (Gamunex, 10%)
    M Ballow
    Division of Allergy Immunology and Pediatric Rheumatologym Kaleida Hralth at The Children s Hospital of Buffalo SUNY Buffalo, Department of Pediatrics, Buffalo, New York 14222, USA
    Vox Sang 84:202-10. 2003
    ..Two clinical studies were conducted to compare the pharmacokinetics of the new product, IGIV-C, 10% (Gamunex, 10%), formulated with glycine, with the licensed solvent-detergent (..
  69. ncbi Conditional weighted residuals (CWRES): a model diagnostic for the FOCE method
    Andrew C Hooker
    Division of Pharmacokinetics and Drug Therapy, Dept of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Box 591, 751 24, Uppsala, Sweden
    Pharm Res 24:2187-97. 2007
    ..Utilizing WRES with the FOCE method may lead to misguided model development/evaluation. We present a new diagnostic tool, the conditional weighted residuals (CWRES), which are calculated based on the FOCE approximation...
  70. ncbi Role of red blood cells in pharmacokinetics of chemotherapeutic agents
    Dirk Schrijvers
    Department of Medical Oncology, AZ Middelheim, Antwerp, Belgium
    Clin Pharmacokinet 42:779-91. 2003
    ..The erythrocyte concentration of mercaptopurine has a prognostic value in the treatment of childhood acute lymphoblastic leukemia. In this review, the role of red blood cells for various anticancer drugs is further discussed...
  71. ncbi Assessment of actual significance levels for covariate effects in NONMEM
    U Wählby
    Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 751 24 Uppsala, Sweden
    J Pharmacokinet Pharmacodyn 28:231-52. 2001
    ..Estimation with FOCE-INTER and the covariate randomization procedure provide means to achieve agreement between nominal and actual significance levels...
  72. ncbi Clinical relevance of pharmacokinetics and pharmacodynamics in cardiac critical care patients
    Federico Pea
    Institute of Clinical Pharmacology and Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy
    Clin Pharmacokinet 47:449-62. 2008
    b>Pharmacokinetics is a discipline aimed at predicting the best dosage and dosing regimen for each single drug in order to ensure and maintain therapeutically effective concentrations at the action sites...
  73. ncbi Pharmacokinetics and its role in small molecule drug discovery research
    G R Jang
    Department of Pharmacokinetics and Drug Metabolism, Amgen Inc, Thousand Oaks, California 91320-1799, USA
    Med Res Rev 21:382-96. 2001
    b>Pharmacokinetics (PK), which describes the disposition of a drug in the body, should be a primary consideration in the selection of a drug candidate, ultimately contributing to its eventual clinical success or failure...
  74. ncbi Physiologically-based pharmacokinetics in drug development and regulatory science
    Malcolm Rowland
    Centre for Pharmacokinetic Research, University of Manchester, United Kingdom
    Annu Rev Pharmacol Toxicol 51:45-73. 2011
    ..Finally, some attention is given to the positioning of PBPK within the drug development and approval paradigm and its future application in truly personalized medicine...
  75. ncbi Assessing antibody pharmacokinetics in mice with in vivo imaging
    Jack Hoppin
    inviCRO, LLC, 2 Oliver St Suite 611, Boston, MA 02109, USA
    J Pharmacol Exp Ther 337:350-8. 2011
    ..Images and analysis results from a case study are presented with a discussion of output data content and relevant informatics gained with this approach to studying antibody pharmacokinetics.
  76. ncbi Gliadin nanoparticles as carriers for the oral administration of lipophilic drugs. Relationships between bioadhesion and pharmacokinetics
    M A Arangoa
    , , Universidad de Navarra, Pamplona, Spain
    Pharm Res 18:1521-7. 2001
    ..These pharmacokinetic modifications were directly related to the bioadhesive capacity of these carriers with the stomach mucosa...
  77. ncbi ADMET in silico modelling: towards prediction paradise?
    Han van de Waterbeemd
    Pfizer Global Research and Development, PDM, Sandwich, Kent CT13 9NJ, UK
    Nat Rev Drug Discov 2:192-204. 2003
    Following studies in the late 1990s that indicated that poor pharmacokinetics and toxicity were important causes of costly late-stage failures in drug development, it has become widely appreciated that these areas should be considered as ..
  78. ncbi The Simcyp population-based ADME simulator
    Masoud Jamei
    Modelling and Simulation Group, Simcyp Limited, Blades Enterprise Centre, Sheffield, UK
    Expert Opin Drug Metab Toxicol 5:211-23. 2009
    ..This review describes the framework and organisation of the simulator and how it combines the different categories of information...
  79. ncbi Application of in silico approaches to predicting drug--drug interactions
    S Ekins
    Lilly Research Laboratories, Lilly Corporate Center, Drop Code 1730, Indianapolis, IN 46285, USA
    J Pharmacol Toxicol Methods 45:65-9. 2001
    ..poor absorption, distribution, metabolism, and excretion (ADME), and the related properties of toxicity and pharmacokinetics are responsible for a large proportion of failures...
  80. ncbi Application of allometric principles for the prediction of pharmacokinetics in human and veterinary drug development
    Iftekhar Mahmood
    Office of Blood Review and Research, Center for Biologic Evaluation and Research, Food and Drug Administration, 1451 Rockville Pike, MD, USA
    Adv Drug Deliv Rev 59:1177-92. 2007
    ..Interspecies scaling is also a very useful tool in veterinary medicine. The knowledge of pharmacokinetics in veterinary medicine is important for dosage selection, particularly in the treatment of large animals such ..
  81. ncbi Physiologically based pharmacokinetics (PBPK)
    Pascal Espie
    UCB Pharma SA, Belgium
    Drug Metab Rev 41:391-407. 2009
    ..In addition, by providing a link between tissue concentrations and toxicological or pharmacological effects, PBPK modeling represents a framework for mechanistic pharmacokinetic-pharmacodynamic models...
  82. ncbi Pharmacokinetic predictions in children by using the physiologically based pharmacokinetic modelling
    F Bouzom
    Technologie Servier, 27 rue Eugene Vignat, BP 11749, 45007 Orléans Cedex 1, France
    Fundam Clin Pharmacol 22:579-87. 2008
    ..Physiologically based pharmacokinetics is one way to integrate the physiological changes occurring in the childhood and to anticipate their impact ..
  83. pmc Sex differences in pharmacokinetics and pharmacodynamics
    Offie P Soldin
    Departments of Medicine, Oncology and Physiology, Center for the Study of Sex Differences, Georgetown University Medical Center, Washington, DC, USA
    Clin Pharmacokinet 48:143-57. 2009
    ..This review summarizes the sex-based differences that impact on pharmacokinetics, and includes a general comparison of clinical pharmacology as it applies to men, women and pregnant women...
  84. ncbi Tailor-made drug treatment for children: creation of an infrastructure for data-sharing and population PK-PD modeling
    Ibrahim Ince
    Department of Pediatric Surgery, Erasmus MC Sophia Children s Hospital, Rotterdam, The Netherlands
    Drug Discov Today 14:316-20. 2009
    ..In addition to modeling of drug disposition (PK) pathways, we emphasize the need for modeling of effect (PD) pathways and the use of a multidisciplinary infrastructure for data-sharing...
  85. ncbi Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studies
    Alberto Larghi
    Division of Internal Medicine, Department of Medicine, Surgery and Dentistry, Ospedale San Paolo, Italy
    Hepatology 36:993-1000. 2002
    ..15 patients with acute hepatitis C (AHC) among 29 healthy volunteers participating in 2 consecutive pharmacokinetics studies...
  86. pmc Modelling approaches to dose estimation in children
    Trevor N Johnson
    Simcyp Ltd, Blades Enterprise Centre, John Street, Sheffield S2 4SU, UK
    Br J Clin Pharmacol 59:663-9. 2005
    ..However, following such an exercise, well-conducted PK-PD or PK studies will still be needed to determine the most appropriate doses for neonates, infants, children and adolescents...
  87. ncbi Considerations in the use of cerebrospinal fluid pharmacokinetics to predict brain target concentrations in the clinical setting: implications of the barriers between blood and brain
    Elizabeth C M de Lange
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden, The Netherlands
    Clin Pharmacokinet 41:691-703. 2002
    ..As non-invasive alternative techniques, positron emission tomography or magnetic resonance spectroscopy may be of added value...
  88. ncbi Drugs in pregnancy. Pharmacokinetics in pregnancy
    M Dawes
    Department of Clinical Pharmacology, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK
    Best Pract Res Clin Obstet Gynaecol 15:819-26. 2001
    b>Pharmacokinetics describes the handling of a drug by the body - how the drug is absorbed, distributed and eliminated and how these processes determine plasma concentrations of the drug...
  89. ncbi Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution
    Patrick Poulin
    Non Clinical Development Drug Safety, Pharmaceuticals Division, F Hoffmann La Roche Ltd, CH 4070 Basel, Switzerland
    J Pharm Sci 91:129-56. 2002
    ..The present study is the first attempt to develop and validate a mechanistic distribution model for predicting rat and human V(ss) of drugs prior to in vivo studies...
  90. ncbi Using the time of maximum effect site concentration to combine pharmacokinetics and pharmacodynamics
    Charles F Minto
    Department of Anaesthesia and Pain Management, Royal North Shore Hospital, Sydney, Australia
    Anesthesiology 99:324-33. 2003
    ..The authors propose an alternative methodology to rationally combine the results of separate pharmacokinetic and pharmacodynamic studies, based on t(peak), the time of peak effect after bolus injection...
  91. ncbi The influence of sex on pharmacokinetics
    Janice B Schwartz
    Institute on Aging and Jewish Home of San Francisco, and University of California, San Francisco, California 94112, USA
    Clin Pharmacokinet 42:107-21. 2003
    ..The relative role of sex on pharmacokinetics as compared to genetics, age, disease, social habits and their potential interactions in the clinical setting ..
  92. ncbi Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis
    Meindert Danhof
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, 2300 RA Leiden, The Netherlands
    Annu Rev Pharmacol Toxicol 47:357-400. 2007
    ..This has yielded models with much-improved properties for extrapolation and prediction. These models constitute a theoretical basis for rational drug discovery and development...
  93. pmc Modelling and PBPK simulation in drug discovery
    Hannah M Jones
    Pfizer Global R and D, Department of Pharmacokinetics, Dynamics and Metabolism, IPC 654, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
    AAPS J 11:155-66. 2009
    ..Specific reference is made to its utility (1) at the lead development stage for the prioritization of compounds for animal PK studies and (2) at the clinical candidate selection and "first in human" stages for the prediction of human PK...
  94. ncbi Effects of food on clinical pharmacokinetics
    B N Singh
    Department of Pharmacy and Administrative Sciences, College of Pharmacy and Allied Health Professions, St John s University, Jamaica, New York, USA
    Clin Pharmacokinet 37:213-55. 1999
    ..A mechanistic understanding of the effects of food may serve as a key to the pharmacokinetic optimisation of patient therapy, both in outpatients and hospitalised patients of various age groups...
  95. ncbi The virtual laboratory approach to pharmacokinetics: design principles and concepts
    Wilhelm Huisinga
    DFG Research Center MATHEON and Freie Universität Berlin, Fachbereich Mathematik und Informatik, Arnimallee 2 6, D 14195 Berlin, Germany
    Drug Discov Today 11:800-5. 2006
    Modeling and simulation in pharmacokinetics has turned into the focus of pharmaceutical companies, driven by the emerging consensus that in silico predictions, combined with in vitro data, have the potential to significantly increase ..
  96. ncbi Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol
    Richard O Day
    School of Medical Sciences, Faculty of Medicine, University of New South Wales and Department of Clinical Pharmacology and Toxicology, St Vincent s Hospital, Sydney, New South Wales, Australia
    Clin Pharmacokinet 46:623-44. 2007
    ..The net effect is an increased degree of hypouricaemia, but the interaction is probably limited to patients with normal renal function or only moderate impairment...
  97. ncbi Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs
    Ingolf Cascorbi
    Institute of Pharmacology, University Hospital Schleswig Holstein, Hospitalstrasse 4, D 24105 Kiel, Germany
    Pharmacol Ther 112:457-73. 2006
    ..variances in the genes of membrane transporters could explain at least in part interindividual differences of pharmacokinetics and clinical outcome of a variety of drugs...
  98. ncbi An evaluation of the utility of physiologically based models of pharmacokinetics in early drug discovery
    Neil Parrott
    F Hoffmann La Roche AG, Pharmaceuticals Division, CH 4070 Bl, Switzerland
    J Pharm Sci 94:2327-43. 2005
    Generic physiologically-based models of pharmacokinetics were evaluated for early drug discovery. Plasma profiles after intravenous and oral dosing were simulated in rat for 68 compounds from six chemical classes...
  99. ncbi Can the pharmaceutical industry reduce attrition rates?
    Ismail Kola
    Basic Research at Merck Research Labs, 126 East Lincoln Avenue, Rahway, New Jersey 07075, USA
    Nat Rev Drug Discov 3:711-5. 2004
  100. ncbi So many studies, too few subjects: establishing functional relevance of genetic polymorphisms on pharmacokinetics
    J Andrew Williams
    Pfizer Global Research and Development, Department of Pharmacokinetics, Dynamics and Metabolism, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
    J Clin Pharmacol 46:258-64. 2006
    Based on current literature, greater clarity in defining the magnitude of polymorphism effects on pharmacokinetics can be achieved by addressing key components of study design, including adequate subject numbers per study group...
  101. ncbi Pharmacokinetics of mycophenolic acid in severe lupus nephritis
    Paungpaga Lertdumrongluk
    Renal Division, Lupus Research Unit, Faculty of Medicine, Department of Medicine, Chulalongkorn University, Bangkok, Thailand
    Kidney Int 78:389-95. 2010
    ..The dosage of the drug was not related to MPA pharmacokinetics. In the mycophenolate mofetil group, however, MPA-area under the curve was positively, and significantly, ..

Research Grants72

  1. PHARMACODYNAMICS OF AGENTS FOR BLADDER CANCER THERAPY
    JESSIE AU; Fiscal Year: 2003
    This competitive renewal application is to define the pharmacokinetics and pharmacodynamics of the drugs commonly used in intravesical therapy, in order to optimize the treatment regimen...
  2. Multi-targeted Countermeasures against Acute and Delayed Effects of OP Exposure
    John A Butera; Fiscal Year: 2013
    ..g. reduced MW, LogP) and would provide one dimensional metabolism, pharmacokinetics, and safety profiles as opposed to co-administering two drugs where development metrics are complicated due ..
  3. Development of VN/14-1 and Related Analogs for Breast Cancer Therapy
    VINCENT COLLINS OFUKA NJAR; Fiscal Year: 2013
    ..which show that the enantiomers in a chiral compound/drug generally show significant differences in their pharmacokinetics (PK), pharmacodynamics (PD) and adverse reactions...
  4. Inhibition of IkK to treat lethal Graft-vs.-Host Disease
    Patrick Flood; Fiscal Year: 2009
    ..Finally, studies are proposed to investigate the pharmacokinetics and pharmacodynamics of the compound in dogs after transplantation...
  5. Bi-functional Therapeutics for Allergy-BFTA
    Swey Shen Chen; Fiscal Year: 2010
    ..its biological equivalents of PIT (bioreactivities;strength/concentration), its safety (adverse effect, ADE), pharmacokinetics (distribution), and pharmacodynamics (efficacies/effectiveness) as the drug substance...
  6. Novel Peptide MPO Inhibitors for Treating Atherosclerosis
    Kirkwood A Pritchard; Fiscal Year: 2012
    ..Aim 2 has two major goals. First, Aim 2 will determine the pharmacokinetics and cytotoxicity of the most effective MPO inhibitors identified in Aim 1...
  7. The Relationship Between STK39, Salt Sensitivity, and HCTZ-induced BP Response
    YEN PEI CHRISTY CHANG; Fiscal Year: 2010
    ..by a team of young investigators with expertise in genetics, ion-transporter physiology, nephrology, pharmacokinetics/pharmacodynamics, and statistical analysis...
  8. Alzheimer's Disease Therapeutic
    Trevor P Castor; Fiscal Year: 2012
    ..1) Specific Aim 1: For selected formulations, radioactive bryostatin 1 will be assayed to determine the pharmacokinetics and tissue distribution...
  9. Small Molecule targeting of NADPH oxidase in neutrophils
    Marie Dominique Filippi; Fiscal Year: 2010
    ..interaction studies, B) mouse neutrophil studies and C) human neutrophil studies (Aim1);test toxicity and pharmacokinetics in vivo and determine the efficacy of NSC23766 and phox-I in acute lung inflammation mouse model (Aim2)...
  10. Efficacy of GABAA a5 receptor inverse agonists in learning impaired rats
    EARL MICHAEL GIBBS; Fiscal Year: 2010
    ..In this SBIR Phase I project, PhysioGenix will determine the efficacy, pharmacokinetics (PK), maximum tolerated dose and potential side-effects of PWZ-029, a benzodiazepine (BZ) compound that may ..
  11. A Novel Thioredoxin Mimetic Prodrug for Prevention of Bronchopulmonary Dysplasia
    Prakash Jagtap; Fiscal Year: 2013
    ..R-908 will now undergo evaluation in a clinically-relevant rat pup model of BPD. Aim #1: Define the pharmacokinetics (PK) of R-908 in newborn rats...
  12. Transplatin: A Novel Agent to Mitigate Cisplatin Toxicity
    Vickram Ramkumar; Fiscal Year: 2013
    ..Aim 3 will determine the pharmacokinetics of transplatin following IV and oral administration...
  13. N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus Infecti
    Aquilur Rahman; Fiscal Year: 2013
    ..the eventual initiation of Phase I clinical trials to determine the maximum tolerated dose, side effects, bioavailability, pharmacokinetics and the starting doses for Phase IIA clinical trials in patients with genital HSV-2 infections.
  14. Improved Adventitial Sirolimus Therapy for Peripheral Artery Restenosis
    KIRK SEWARD; Fiscal Year: 2010
    ..We will choose a therapeutic, non-toxic dose to use in Specific Aim 2, in which we will study the pharmacokinetics of adventitially delivered sirolimus...
  15. Novel Therapy for Preeclampsia
    James W Larrick; Fiscal Year: 2012
    ..Phase II work will focus on obtaining the preclinical data necessary for submission of an IND. Pharmacokinetics and toxicity studies, as well as animal studies to demonstrate efficacy, will be performed...
  16. Antibody-mediated Gene Therapy for the Treatment of Cancer
    TRACY RUTH DANIELS-WELLS; Fiscal Year: 2013
    ..Aim 3: Evaluation of toxicity, pharmacokinetics, and anti-tumor activity in animal models...
  17. Treatment of Inflammatory Bowel Disease with Ceramidase Inhibitors
    Lynn W Maines; Fiscal Year: 2012
    ..To synthesize and evaluate the toxicity and pharmacokinetics of novel ceramidase inhibitors...
  18. Novel CTD inhibitors with synthetic lethality to oncogenic Ras for cancer therapy
    Bingliang Fang; Fiscal Year: 2013
    ..However, in vivo evaluation of the pharmacokinetics, antitumor efficacy, and safety of oncrasin compounds is necessary before they can be evaluated clinically...
  19. Role of poly (ADP-ribose) polymerase 1 (PARP-1) in experimental colitis
    Claire Larmonier; Fiscal Year: 2013
    ..Such studies are critical in guiding future development of therapeutics targeting PARP1, with proper pharmacokinetics and pharmacodynamics...
  20. Therapeutics for Drug-Resistant Bacteria: Myxopyronins
    Richard H Ebright; Fiscal Year: 2013
    ..in small-animal models of infection, and analogs of highest promise will be evaluated for bioavailability, pharmacokinetics, toxicity, and ability to scale synthesis. Primary target pathogens include: M...
  21. New drug VS-110 for treating inflammatory bowel diseases
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2013
    ..of VS-110 into Phase II IND-enabling studies including VS-110 synthesis scale-up, process development and pharmacokinetics, metabolism, safety and toxicology...
  22. NOVEL PET AGENT FOR MYOCARDIAL PERFUSION IMAGING
    Vijay Sharma; Fiscal Year: 2013
    ..Additionally, current SPECT tracers also suffer from shortcomings in pharmacokinetics, myocardial extraction, redistribution of the radiotracer to non-targeted tissues over time, and non-..
  23. New drug Vida-5 for treating chronic kidney disease progression
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2011
    ..of Vida-5 into Phase II IND-enabling studies including Vida-5 synthesis scale-up, process development and pharmacokinetics, metabolism, safety and toxicology...
  24. Novel drug VS-105 for treatment of diabetic nephropathy
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2012
    ..of VS-105 into Phase II IND-enabling studies including VS-105 synthesis scale-up, process development and pharmacokinetics, metabolism, safety and toxicology...
  25. Use of Phosphodiesterase Inhibitors to Evaluate the Pathobiology of CF
    JENNIFER L TAYLOR-COUSAR; Fiscal Year: 2013
    ..1) Establish safety and tolerability of systemic PDEi administration to subjects with CF 2) Demonstrate that pharmacokinetics of systemic PDEi administration in patients with CF are equivalent to those without CF and 3) Establish the ..
  26. Nanomedicine and NeuroAIDS
    Howard E Gendelman; Fiscal Year: 2013
    ..the development of long-acting injectable nanoformulated ART (nanoART) with superior biodistribution and pharmacokinetics over native drugs...
  27. Double Humanization of Liver and Blood in Mice
    ELIZABETH MARIE WILSON; Fiscal Year: 2012
    ..drug metabolism and pharmacokinetics, drug-drug interactions, toxicology and gene therapy among others...
  28. Theranostic Nanomedicine for Breast Cancer Prevention and Image-Guided Therapy
    Prakash R Rai; Fiscal Year: 2011
    ..This will allow us to establish the pharmacokinetics of TNC and its biodistribution, disease assessment and the initiation of light treatments thus helping ..
  29. Development of Montelukast Delivery System for Childhood Asthma
    Je Phil Ryoo; Fiscal Year: 2013
    ..The formulation of NAL6336 has been well developed. In the proposed study, we will compare the pharmacokinetics profile of NAL6336 ODF and montelukast oral suspension in rats, and assess the irritation and safety of ..
  30. Combination therapies for chronic HBV, liver disease and cancer
    Mark A Feitelson; Fiscal Year: 2012
    ..To do so, the lab will assess the pharmacokinetics (PK), antiviral efficacy and toxicity of drug combinations in primary human hepatocytes and in HepG2 cells ..
  31. Organismal Radioprotection Through Pharmacological Quiescence
    JOHN S CHANT; Fiscal Year: 2010
    ..In aim 1, we will test several additional CDK small molecule inhibitors with differing pharmacokinetics in vitro and in vivo to identify the optimal dosing schedule for maximal radioprotection...
  32. Inhibition of S14 by Conjugated Linoleic Acid in Advanced Solid Tumor Patients
    Raymond P Perez; Fiscal Year: 2010
    ..Dose titration continues until a plateau in S14 response is observed, unless clinical toxicities or pharmacokinetics require stopping before that point...
  33. Novel Drug VS-105 for Treatment of Osteoporosis
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2013
    ..of VS-105 into Phase II IND-enabling studies including VS-105 synthesis scale-up, process development and pharmacokinetics, metabolism, safety and toxicology...
  34. Developing Immunotherapeutics for Methamphetamine Abuse
    THOMAS RICHARD KOSTEN; Fiscal Year: 2010
    ..The ability of the vaccine to alter MA pharmacokinetics and metabolism will be assessed, as well as inhibition of reinstatement of MA self-administration...
  35. Preclinical studies of a heroin/morphine vaccine for opiate addiction
    Paul R Pentel; Fiscal Year: 2013
    ..Because heroin pharmacokinetics is complex, particular attention will be paid to characterizing and quantitating M-TT effects on heroin and ..
  36. Developing a New Antioxidant Activator to Intervene in Lung Inflammatory Diseases
    JOHN WILLIMANN; Fiscal Year: 2009
    ..2) Determine the pharmacokinetics and Nrf2-selectivity of the active oil...
  37. Novel Therapeutics for Neurotropic Alphaviruses
    David J Miller; Fiscal Year: 2013
    ..identify molecular target(s) responsible for their antiviral activity;(3) analyze the in vivo pharmacokinetics and efficacy of candidate antivirals, including combination treatment with neuroprotective agents;and (4) ..
  38. Pilot Clinical Study in Renal Transplantation
    Weizhong Cai; Fiscal Year: 2010
    ..In addition, a Phase Ib clinical trial evaluating pharmacokinetics and safety of BB3 in stable adult patients on chronic hemodialysis has also been completed...
  39. A Targeted Preemptive Approach to Addressing Mitochondrial Toxicity of Nucleoside
    John K Buolamwini; Fiscal Year: 2013
    ..and 3) study biopharmaceutic and pharmacokinetic properties of selected prodrugs and their influence on the pharmacokinetics of nucleoside drugs of interest...
  40. Pharmacology of Antiretroviral Nanoparticle Micelles
    Christopher J Destache; Fiscal Year: 2010
    ..The pharmacodynamics and pharmacokinetics of combination ARV NP will be determined using in vitro and in vivo systems over extended time periods as ..
  41. Fully Biodegradable Polymersome-encapsulated Hemoglobin as a Novel Nanoparticle-b
    PAIMAN PETER GHOROGHCHIAN; Fiscal Year: 2010
    ..PEH dispersions that meet our feasibility criteria will be advanced to Phase II to determine their pharmacokinetics, biodistribution, toxicology and tissue oxygenation in small-animal models...
  42. Multivalent Vaccine for Opiate Addiction
    Paul R Pentel; Fiscal Year: 2012
    ..Vaccines which alter drug pharmacokinetics have shown substantial preclinical and preliminary clinical evidence of efficacy for nicotine and cocaine ..
  43. Developing a prediction model for vincristine-induced peripheral neuropathy
    Jamie L Renbarger; Fiscal Year: 2010
    ..Recently published data indicate that vincristine pharmacokinetics may be associated with long-term outcomes in children with acute lymphoblastic leukemia (ALL)...
  44. COMBINATORIAL-DESIGNED NANO-PLATFORMS TO OVERCOME TUMOR DRUG RESISTANCE
    Zhenfeng Duan; Fiscal Year: 2013
    ..of tumor targeting efficacy, residence, biodistribution profiles, and evaluation of non- compartmental pharmacokinetics in SK0V3TR and NIH-H69AR tumor xenograft models after systemic administration;(4) further refinement of "hits"..
  45. Testing Compounds that Increase SMN levels for Efficacy in Mouse Models of SMA
    Elliot J Androphy; Fiscal Year: 2010
    ..Aim 1 will test the drug-like properties, pharmacokinetics and acute toxicology of active compounds that emerge from these structure-activity relationship studies...
  46. Depot calcineurin inhibitors to prevent graft rejection
    Thomas J Smith; Fiscal Year: 2010
    ..sustained release CsA in this Phase 2 proposal because it was easier to crystallize and demonstrated superior pharmacokinetics when tested in rats...
  47. Theranostic Nanomedicine for Breast Cancer Prevention and Image-Guided Therapy
    Prakash R Rai; Fiscal Year: 2013
    ..This will allow us to establish the pharmacokinetics of TNC and its biodistribution, disease assessment and the initiation of light treatments thus helping ..
  48. In vivo imaging of encapsulated stem cells in mouse models of tumor resection
    Khalid A Shah; Fiscal Year: 2013
    ..imaging (BLI) markers into MSC and GBMs will allow us to follow GBM cell invasion, fate of MSC and pharmacokinetics of therapeutic proteins and their efficacy by in vivo BLI, intravital microscopy (IVM), magnetic resonance ..
  49. Developing a New Therapeutic for the Treatment of Invasive Aspergillosis
    Mitchell W Mutz; Fiscal Year: 2013
    ..3) Screen and select these compounds for low immunosuppression, potent antifungal activity, and favorable pharmacokinetics. The impact of this work will be to utilize a structural biologic approach to design, synthesize, and test ..
  50. Developing Novel Dual CRF-R1/Orexin-1 Receptor Antagonists for Tobacco Dependence
    Belew Mekonnen; Fiscal Year: 2011
    ..to a final lead optimization campaign focused on identifying pre- clinical leads with well-balanced in vivo pharmacokinetics (PK) parameters for key behavioral as well as pharmacological POC studies in rodent addiction and relapse ..
  51. Development of New Therapeutics for Pancreatic Cancer Management
    RICHARD JOSEPH PIETRAS; Fiscal Year: 2013
    ..cancer cell xenografts in nude mouse models to assess antitumor activity and exploratory study of drug pharmacokinetics. Endocrine- metabolic effects of metformin analogs will also be studied in vivo in an established insulin-..
  52. Radiocontrast Nephropathy: Redox Degradation Catalyst and Nitric Oxide Donor
    ZSUZSANNA KINGA ZSENGELLER; Fiscal Year: 2013
    ..Aim #2: Establish the pharmacokinetics (PK) of R-100 in a rodent model of CIN We will carry out PK studies in rodents exposed to the same conditions ..
  53. New Peptides for the Treatment of Multiple Sclerosis
    Christine Beeton; Fiscal Year: 2013
    ..Under Specific Aim 3 we will evaluate the most potent and selective ShK analogs in vivo for pharmacokinetics, immunogenicity, safety, and efficacy. This project will generate novel peptide blockers of Kv1...
  54. Silencing cardiac-specific microRNAs to prevent pathological remodeling in conges
    MATTHEW SWAN LAWRENCE; Fiscal Year: 2011
    ..The current proposal focuses on evaluating the biodistribution, pharmacokinetics and pharmacokinetic/ pharmacodynamics (PK/PD) of antimiR-208a vs...
  55. Fatty Acid Synthase Inhibitors As Broad Spectrum Anti-Flaviviral Therapeutics
    Glenn Randall; Fiscal Year: 2013
    ..Further drug evaluation assessing pharmacokinetics, pharmacodynamics, and various toxicity assays will be performed to advance these compounds toward IND filing...
  56. Transferrin Conjugates for Oral Protein Drug Delivery
    Wei Chiang Shen; Fiscal Year: 2013
    ..peptide spacers will be designed and inserted between the two domains in the fusion proteins to improve pharmacokinetics, bioavailability and bioactivity...
  57. Bifunctional Redox Agent for the Treatment of PPHN
    GARRY JOHN SOUTHAN; Fiscal Year: 2011
    ..in each species, and provide the regulatory basis for a dose range to be explored for safety, tolerance, and pharmacokinetics in human neonates...
  58. Chemoprevention of Pancreatic Cancer by Capsaicin
    Sanjay K Srivastava; Fiscal Year: 2013
    ..mice models of pancreatic intraepithelial neoplasia (PanINs) respectively and its bioavailability and pharmacokinetics. Successful completion of this project will support the development and clinical application of capsaicin for ..
  59. Malaria and the safety of iron interventions: absorption and NTBI
    Gary M Brittenham; Fiscal Year: 2012
    This research will determine the effects of acute infection with Plasmodium falciparum on the absorption, pharmacokinetics and metabolism of iron from iron supplements and other Iron preparations in women of childbearing age...
  60. Preventing lethal hemorrhagic fever caused by hantaviruses by preserving endothel
    ALAN L MUELLER; Fiscal Year: 2012
    ..Specific Aim 1: Investigate Slit2N pharmacokinetics (PK) and 7-day tolerability in hamsters...
  61. Development of New Molecular Probes for Diagnostic Imaging of Atherosclerosis
    KAREN CATHERIN BRILEY SAEBO; Fiscal Year: 2010
    ..MDA2 was chosen as the targeting moiety due to availability. In Aim 2 the pharmacokinetics, biodistribution, and MR imaging efficacy of the various oxLDL targeting moieties (MDA2, EO6, and IK17) will ..
  62. Pharmacogenomics of Tacrolimus and New Onset Diabetes After Kidney Transplant
    Kelly A Birdwell; Fiscal Year: 2013
    ..associated with abnormal glucose metabolism in kidney transplant recipients are associated with tacrolimus pharmacokinetics. Aim 3 will characterize relationships between candidate genes implicated in tacrolimus disposition and/or ..
  63. Compounds to treat Helicobacter pylori infection
    Kenneth Coleman; Fiscal Year: 2013
    ..ensure that a clear SAR with respect to potency is observed and that subsequent optimization for safety and pharmacokinetics is attainable...
  64. Phase I Study to Evaluate Safety and Toxicity of EGCG in HIV-1-Infected Subjects
    Christina L Nance; Fiscal Year: 2011
    ..Therefore, the purpose of this study is to determine the safety, toxicity, pharmacokinetics, HIV-1 viral load change, and dosage of EGCG administered orally once (600 or 1000mg) or twice (800mg) daily ..
  65. Malaria treatment outcomes and pharmacokinetics in HIV-infected pregnant women
    MYAING MYAING NYUNT; Fiscal Year: 2010
    ..of the drug in pregnant women in many endemic countries following the WHO recommendation, knowledge on the pharmacokinetics, safety and efficacy of artemether-lumefantrine is extremely limited in the pregnant population, especially ..
  66. Betahistine: Novel Therapeutic in Attention Deficit Hyperactivity Disorder
    CHARLES PIERCE; Fiscal Year: 2009
    ..The immediate goal of this Phase I SBIR is to determine safety, tolerability, and pharmacokinetics of betahistine single-doses >48 mg and to determine a dose-response for improving attention and ..
  67. Azithromycin to prevent BPD in Ureaplasma-infected Preterms: Single Dose PK study
    Rose Viscardi; Fiscal Year: 2009
    ..Currently, the pharmacokinetics, safety, and biologic effects of azithromycin in the preterm population are unknown...
  68. Improving the efficacy of anti-nicotine immunotherapy
    Alexey G Mukhin; Fiscal Year: 2010
    ..effects of nicotine, anti- nicotine immunotherapy is a relatively new approach that directly targets the pharmacokinetics of nicotine...
  69. The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology
    Christina L Aquilante; Fiscal Year: 2010
    ..Currently, the extent to which genetic variation influences interindividual variability in sitagliptin pharmacokinetics (i.e., disposition) and pharmacodynamics (i.e., response) is not known...
  70. ARIZONA CENTER FOR PHYTOMEDICINE RESEARCH (ACPRX)
    Janet Funk; Fiscal Year: 2004
    ..active compounds or mixtures of compounds, mechanisms of action, oral bioavailability, pharmacodynamics, and pharmacokinetics. The effect of the botanicals on production of anti-inflammatory mediators will be evaluated in vitro, as ..
  71. Drug Interactions and Bioavailability of Cranberry
    Jennifer Donovan; Fiscal Year: 2005
    ..aims of this research are 1) to evaluate the potential for CB-drug interactions and 2) to determine the pharmacokinetics and renal clearance of four major CB flavonoids...
  72. ART PHARMACOKINETICS IN SEVERELY MALNOURISHED HIV-INFECTED CHILDREN
    Ericka Hayes; Fiscal Year: 2009
    The objective of this project is to understand how severe malnutrition affects the pharmacokinetics of highly active antiretroviral therapy (HAART) as well as antioxidant capacity and mitochondrial integrity in HIV infected children ..