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 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
  2. 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
  3. doi 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
  4. doi 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. doi 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

Detail Information

Publications242 found, 100 shown here

  1. 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...
  2. 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...
  3. doi 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...
  4. doi 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...
  5. 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...
  6. 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 ..
  7. 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.
  8. 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.
  9. 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...
  10. doi 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...
  11. 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)...
  12. 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...
  13. doi 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...
  14. doi 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...
  15. 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...
  16. doi 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...
  17. 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...
  18. 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...
  19. 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...
  20. ncbi Population pharmacokinetics II: estimation methods
    Ene I Ette
    Vertex Pharmaceuticals, Inc, Cambridge, MA, USA
    Ann Pharmacother 38:1907-15. 2004
    ....
  21. 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 ..
  22. 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 ..
  23. 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 (..
  24. 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...
  25. 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...
  26. 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...
  27. 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...
  28. 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...
  29. doi 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.
  30. doi 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...
  31. 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 ..
  32. 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...
  33. doi 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...
  34. 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...
  35. 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...
  36. doi 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...
  37. 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...
  38. 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 ..
  39. doi 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 ..
  40. doi 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...
  41. 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...
  42. 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...
  43. 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...
  44. doi 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...
  45. 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...
  46. 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...
  47. 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...
  48. 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...
  49. 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...
  50. doi 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...
  51. 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 ..
  52. 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...
  53. 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.
  54. 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...
  55. 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...
  56. 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...
  57. 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...
  58. 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 ..
  59. 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...
  60. 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...
  61. 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
  62. 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
    ....
  63. 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
    ....
  64. doi 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, ..
  65. ncbi The lasso--a novel method for predictive covariate model building in nonlinear mixed effects models
    Jakob Ribbing
    Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, Uppsala University, Box 591, 75124 Uppsala, Sweden
    J Pharmacokinet Pharmacodyn 34:485-517. 2007
    Covariate models for population pharmacokinetics and pharmacodynamics are often built with a stepwise covariate modelling procedure (SCM)...
  66. 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...
  67. ncbi Integrating in vitro ADMET data through generic physiologically based pharmacokinetic models
    David E Leahy
    Cyprotex Discovery Limited, Macclesfield, Cheshire, UK
    Expert Opin Drug Metab Toxicol 2:619-28. 2006
    ..model, Cloe PK) (Cyprotex), which is parameterised for human and rat physiology, to the estimation of plasma pharmacokinetics, are summarised in this paper...
  68. ncbi Evaluation of bioequivalence of highly variable drugs using clinical trial simulations. II: Comparison of single and multiple-dose trials using AUC and Cmax
    A A el-Tahtawy
    Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, Maryland 20857, USA
    Pharm Res 15:98-104. 1998
    ..The main methodology was Monte Carlo simulation, and we also used deterministic simulation, and examination of clinical trials. The results are compared with those previously observed for Cmax (maximum concentration.)..
  69. ncbi Gamma generalized linear models for pharmacokinetic data
    Ruth Salway
    Department of Mathematical Sciences, University of Bath, Bath BA2 7AY, UK
    Biometrics 64:620-6. 2008
    ..The methods are applied to data from 12 individuals following administration of the antiasthmatic agent theophylline...
  70. ncbi Uncertainty factors for chemical risk assessment: interspecies differences in the in vivo pharmacokinetics and metabolism of human CYP1A2 substrates
    K Walton
    Clinical Pharmacology Group, Biomedical Sciences Building, University of Southampton, Bassett Crescent East, SO16 7PX, Southampton, UK
    Food Chem Toxicol 39:667-80. 2001
    ..This work supports the need to replace the generic default factors by a compound-related value derived from specific, relevant, quantitative data; this would result in more relevant and reliable non-cancer risk assessments...
  71. doi Clinical trial simulation: a review
    N Holford
    Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand
    Clin Pharmacol Ther 88:166-82. 2010
    ..This will take advantage of optimizing the experimental design and leave the task of evaluating the probable real-world performance of a limited number of candidate trial designs and analysis procedures...
  72. ncbi Pharmacokinetics of the oral direct renin inhibitor aliskiren alone and in combination with irbesartan in renal impairment
    Sujata Vaidyanathan
    Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
    Clin Pharmacokinet 46:661-75. 2007
    ..This study assessed the effects of renal impairment on the pharmacokinetics and safety of aliskiren alone and in combination with the angiotensin receptor antagonist irbesartan.
  73. ncbi Effect of cationic carriers on the pharmacokinetics and tumor localization of nucleic acids after intravenous administration
    Holger K de Wolf
    Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands
    Int J Pharm 331:167-75. 2007
    ..Rather, the benefits are arising from carrier-induced changes in the intratumoral fate of the nucleic acids...
  74. ncbi New mathematical methods in pharmacokinetic modeling
    Maria Durisova
    Institute of Experimental Pharmacology, Slovak Academy of Sciences, 841 04 Bratislava 4, Slovak Republic
    Basic Clin Pharmacol Toxicol 96:335-42. 2005
    In recent years, several new methods for the mathematical modeling have gradually emerged in pharmacokinetics, and the development of pharmacokinetic models based on these methods has become one of the most rapidly growing and exciting ..
  75. ncbi Bridging the gap: ageing, pharmacokinetics and pharmacodynamics
    Dominick G A Burton
    School of Pharmacy and Biomolecular Science, University of Brighton, Cockcroft Building, Brighton, BN2 4GJ, UK
    J Pharm Pharmacol 57:671-9. 2005
    Changes in pharmacokinetics and pharmacodynamics in elderly patients generally result in an increase in the incidence of drug toxicity and adverse drug reactions...
  76. doi Population pharmacokinetics of oral risperidone in children, adolescents and adults with psychiatric disorders
    An Thyssen
    Johnson and Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica NV, B 2340 Beerse, Belgium
    Clin Pharmacokinet 49:465-78. 2010
    ..The pharmacokinetic profile of risperidone is well documented in adults. In this study, the pharmacokinetics of oral risperidone in children and adolescents were investigated along with population pharmacokinetics in ..
  77. ncbi Impact of genetic polymorphisms in CYP2C9 and CYP2C19 on the pharmacokinetics of clinically used drugs
    Takeshi Hirota
    Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    Drug Metab Pharmacokinet 28:28-37. 2013
    ..This review summarizes the currently available important information on this topic...
  78. doi Theoretical versus empirical allometry: Facts behind theories and application to pharmacokinetics
    Iftekhar Mahmood
    Division of Hematology, Office of Blood Review and Research OBRR, Center for Biologic Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA
    J Pharm Sci 99:2927-33. 2010
    ..enough evidence from experimental data that negate the notion of fixed exponents in biology, physiology, and pharmacokinetics. In short, the notion of a fixed exponent is theoretical and there is no evidence that the exponent of a ..
  79. ncbi Role of population pharmacokinetics in drug development. A pharmaceutical industry perspective
    E Samara
    Department of Pharmacokinetics and Biopharmaceutics, Abbott Laboratories, Abbott Park, Illinois, USA
    Clin Pharmacokinet 32:294-312. 1997
    ..However, several important issues remain to be resolved (such as the optimal study design, quality of the data and user-friendly software) which could determine the future role of the population approach in drug development...
  80. pmc Food protein-stabilized nanoemulsions as potential delivery systems for poorly water-soluble drugs: preparation, in vitro characterization, and pharmacokinetics in rats
    Wei He
    Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People s Republic of China
    Int J Nanomedicine 6:521-33. 2011
    ..It is concluded that an oil/water nanoemulsion system with good biocompatibility can be prepared by using food proteins as emulsifiers, allowing better and more rapid absorption of lipophilic drugs...
  81. ncbi Software for population pharmacokinetics and pharmacodynamics
    L Aarons
    School of Pharmacy and Pharmaceutical Sciences, University of Manchester, England
    Clin Pharmacokinet 36:255-64. 1999
    ..Although robustness and reliability are important concerns, they were not addressed in the present review. Most of the programs surveyed are in continual development...
  82. ncbi Applications of population pharmacokinetics in current drug labelling
    J Z Duan
    Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
    J Clin Pharm Ther 32:57-79. 2007
    The application of population pharmacokinetics (PopPK) appears increasingly in drug labelling. The current study was to examine the use of PopPK in dose recommendation in drug-product labels.
  83. ncbi Pharmacokinetics and metabolism in early drug discovery
    D A Smith
    Pfizer Central Research, Department of Drug Metabolism, Sandwich, Kent, CT13 9NJ, UK
    Curr Opin Chem Biol 3:373-8. 1999
    ..Through linking of in silico and in vitro methods, considerable progress has recently been made towards this future perspective. Despite this progress, these approaches do not yet replace in vivo methods...
  84. ncbi Chirality and pharmacokinetics: an area of neglected dimensionality?
    Andrew J Hutt
    Department of Pharmacy, King s College London, UK
    Drug Metabol Drug Interact 22:79-112. 2007
    ....
  85. ncbi Prescribing medications in pediatrics: concerns regarding FDA approval and pharmacokinetics
    Emily Novak
    Yale University School of Nursing, New Haven, CT, USA
    Pediatr Nurs 33:64-70. 2007
    ..a common guideline for prescribing "off-label" in pediatrics, but must be used in combination with multiple respected pediatric resources and with full knowledge of pharmacokinetics in children, particularly in young children.
  86. ncbi Parametric and nonparametric population methods: their comparative performance in analysing a clinical dataset and two Monte Carlo simulation studies
    Aida Bustad
    Laboratory of Applied Pharmacokinetics, USC Keck School of Medicine, Los Angeles, California, USA
    Clin Pharmacokinet 45:365-83. 2006
    ....
  87. ncbi Improving predictive modeling in pediatric drug development: pharmacokinetics, pharmacodynamics, and mechanistic modeling
    William Slikker
    Office of Research, National Center for Toxicological Research FDA, 3900 NCTR Road, Jefferson, Arkansas 72079 9502, USA
    Ann N Y Acad Sci 1053:505-18. 2005
    ..Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development...
  88. ncbi Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations
    Imke H Bartelink
    Department of Pharmacy, University Medical Center, Utrecht, The Netherlands
    Clin Pharmacokinet 45:1077-97. 2006
    ..The integration of these guidelines, and combining them with pharmacodynamic effects, should be considered and could form a basis for further study...
  89. 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...
  90. ncbi Pharmacokinetics and physiologically-based pharmacokinetic modeling of nanoparticles
    Raymond S H Yang
    Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
    J Nanosci Nanotechnol 10:8482-90. 2010
    ..As toxicology is a continuum of pharmacokinetics and pharmacodynamics, this is a review of recent advances on pharmacokinetics and physiologically-based ..
  91. ncbi Lumping in pharmacokinetics
    Celine Brochot
    INERIS, Institut National de l Environnement Industriel et des Risques, Experimental Toxicology Unit, Parc Alata BP2, 60550 Verneuil en Halatte, France
    J Pharmacokinet Pharmacodyn 32:719-36. 2005
    ..presenting the theory, we study, here, through practical examples, the potential of such methods in toxico/pharmacokinetics. As a tutorial, we first simplify a 2-compartment pharmacokinetic model by symbolic lumping...
  92. doi Resurgence in the use of physiologically based pharmacokinetic models in pediatric clinical pharmacology: parallel shift in incorporating the knowledge of biological elements and increased applicability to drug development and clinical practice
    Trevor N Johnson
    Simcyp Limited, Sheffield, UK
    Paediatr Anaesth 21:291-301. 2011
    ....
  93. ncbi Information tools for exploratory data analysis in population pharmacokinetics
    O Petricoul
    UPRES EA-3286, Faculty of Pharmacy, Marseille, France
    J Pharmacokinet Pharmacodyn 28:577-99. 2001
    ..The rationale for using these indexes is shown using simulated and real data...
  94. ncbi Numerical simulation of local pharmacokinetics of a drug after intravascular delivery with an eluting stent
    Dmitri V Sakharov
    Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands
    J Drug Target 10:507-13. 2002
    We use mathematical modelling to delineate the influence of two important factors on local pharmacokinetics of a drug delivered via an eluting stent, namely: (1) diffusional resistance of a stent coating, and (2) reversible binding of a ..
  95. doi 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...
  96. ncbi Facilitation of drug evaluation in children by population methods and modelling
    Michel Tod
    Department of Pharmacy toxicology, Hopital Cochin Saint Vincent de Paul, Paris, FranceEA 3738, Universite Lyon 1, Universite de Lyon, Lyon, France
    Clin Pharmacokinet 47:231-43. 2008
    The pharmacokinetics and pharmacodynamics of drugs are different in adult and paediatric populations, the latter being particularly heterogeneous...
  97. ncbi Essentials for starting a pediatric clinical study (1): Pharmacokinetics in children
    Tsuyoshi Yokoi
    Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Kanazawa University, Japan
    J Toxicol Sci 34:SP307-12. 2009
    ..function changes drastically by age, drug therapy should be arranged according to the age-related changes in pharmacokinetics of its age...
  98. doi Applications of physiologically based absorption models in drug discovery and development
    Neil Parrott
    F Hoffmann La Roche Ltd Pharmaceuticals Division, Pharma Research Non Clinical Development, Non Clinical Drug Safety, Basel, Switzerland
    Mol Pharm 5:760-75. 2008
    ....
  99. ncbi Pharmacokinetics of high-dose chemotherapy
    Y Nieto
    BMT Programs at the University of Colorado, USA
    Bone Marrow Transplant 33:259-69. 2004
    ..This variation has been recognized to be due, in part, to the wide variation in the pharmacokinetics (PK) of high-dose chemotherapy (HDC)...
  100. ncbi A framework for assessing inter-individual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: A tale of 'bottom-up' vs 'top-down' recognition
    Masoud Jamei
    Simcyp Limited, Sheffield, UK
    Drug Metab Pharmacokinet 24:53-75. 2009
    ..of the drive to decrease this failure rate in drug development involves attempts to use physiologically-based pharmacokinetics 'bottom-up' modeling and simulation to optimize molecular features with respect to the absorption, ..
  101. doi Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma
    Douglas A Stewart
    Department of Oncology and Medicine, Tom Baker Cancer Centre, Calgary, Alberta, Canada
    Biol Blood Marrow Transplant 15:39-46. 2009
    ..Plerixafor was safe and effective in mobilizing CD34(+) cells for transplantation...

Research Grants83

  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. Molecular mechanism of antiangiogenic properties of gold nanoparticle
    Priyabrata Mukherjee; Fiscal Year: 2010
    ..Also to determine the toxicity, pharmacokinetics, metabolism of AuNP and finally test its efficacy as anti-angiogenic agent to inhibit tumor growth and ..
  3. Localized modulation of RPE P-gp/MRP activity for back-of-the-eye drug delivery
    Soumyajit Majumdar; Fiscal Year: 2007
    ..efflux proteins, P- gp and/or MRP, expressed on the retinal pigmented epithelium (RPE), and thus alter ocular pharmacokinetics of systemically/intravitreally co-administered substrates...
  4. Azithromycin to prevent BPD in Ureaplasma-infected Preterms: Single Dose PK study
    Rose Viscardi; Fiscal Year: 2007
    ..Currently, the pharmacokinetics, safety, and biologic effects of azithromycin in the preterm population are unknown...
  5. 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...
  6. Multivalent Vaccine for Opiate Addiction
    Paul R Pentel; Fiscal Year: 2010
    ..Vaccines which alter drug pharmacokinetics have shown substantial preclinical and preliminary clinical evidence of efficacy for nicotine and cocaine ..
  7. Movement-Responsive Cage for Simultaneous Pharmacology Studies in MiniPigs
    Douglas Mann; Fiscal Year: 2007
    ..cytochrome P450 enzymes are so homologous that pigs should be the preferred model for drug metabolism and pharmacokinetics studies. Yet, pigs are under-utilized...
  8. K777 for treatment of Chagas Disease: IND-enabling Studies and IND Submission
    SHING CHANG; Fiscal Year: 2010
    ..IND) application, the First in Man Phase I dose escalation clinical trial to assess safety, tolerability and pharmacokinetics after a single oral dose will be conducted in the United States in healthy volunteers...
  9. Investigating the Role of Adipocytes on Leukemia Relapse
    STEVEN DAVID MITTELMAN; Fiscal Year: 2010
    ..Alternatively, it may be an effect of obesity to confound the leukemia treatment, possibly due to altered pharmacokinetics of chemotherapeutic agents...
  10. Pilot Trial of Bumetanide for Neonatal Seizures
    JANET SUSAN SOUL; Fiscal Year: 2010
    ..2) Evaluate the pharmacokinetics and safety of bumetanide (BTN) in newborns with refractory seizures caused by HIE in a Phase I Trial...