Genomes and Genes
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.
Publications195 found, 100 shown here
- Using pharmacokinetic-pharmacodynamic relationships to predict the effect of poor complianceJean Pierre Boissel
Department of Clinical Pharmacology, Claude Bernard University and Teaching Hospital, Lyon, France
Clin Pharmacokinet 41:1-6. 2002..Forgiveness is the property of a drug which, when compared with another medicine with different pharmacokinetics and/or concentration-effect relationships, blunts the consequences of missing one or two doses in a row, or ..
- Pharmacokinetic changes in critical illnessBradley A Boucher
Department of Pharmacy, University of Tennessee Health Science Center, 26 South Dunlap, Room 210, Memphis, TN 38163, USA
Crit Care Clin 22:255-71, vi. 2006Physiologic alterations in critically ill patients can significantly affect the pharmacokinetics of drugs used in the critically ill patient population...
- The role of permeability in drug ADME/PK, interactions and toxicity--presentation of a permeability-based classification system (PCS) for prediction of ADME/PK in humansUrban Fagerholm
Clinical Pharmacology, AstraZeneca R and D Sodertalje, S 151 85, Sodertalje, Sweden
Pharm Res 25:625-38. 2008....
- PK/PD modelling and beyond: impact on drug developmentDouwe 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...
- Population pharmacokinetics III: design, analysis, and application of population pharmacokinetic StudiesEne 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...
- Tailor-made drug treatment for children: creation of an infrastructure for data-sharing and population PK-PD modelingIbrahim 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...
- Prediction of drug clearance in children: impact of allometric exponents, body weight, and ageIftekhar 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...
- 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...
- Sex differences in pharmacokinetics and pharmacodynamicsOffie 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...
- When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderlyKlaus 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...
- Pharmacokinetic predictions in children by using the physiologically based pharmacokinetic modellingF 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 ..
- Modelling approaches to dose estimation in childrenTrevor 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...
- Mechanism-based concepts of size and maturity in pharmacokineticsB 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...
- Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studiesAlberto 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...
- Challenges and obstacles of ocular pharmacokinetics and drug deliveryArto 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.
- Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysisMeindert 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...
- The influence of sex on pharmacokineticsJanice 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 ..
- Impact of OATP transporters on pharmacokineticsA 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 ..
- Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticlesDonald 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...
- 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
- Development and evaluation of a generic physiologically based pharmacokinetic model for childrenAndrea N Edginton
Competence Center Systems Biology, Bayer Technology Services GmbH, Leverkusen, Germany
Clin Pharmacokinet 45:1013-34. 2006....
- Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorptionJoseph 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...
- In vivo SPECT and real-time gamma camera imaging of biodistribution and pharmacokinetics of siRNA delivery using an optimized radiolabeling and purification procedureOlivia M Merkel
Department of Pharmaceutics and Biopharmacy, Philipps Universitat Marburg, Ketzerbach 63, 35037 Marburg, Germany
Bioconjug Chem 20:174-82. 2009..This optimization and proof of principle study demonstrates that biodistribution and pharmacokinetics of siRNA and the corresponding polyplexes can be determined using SPECT, leading to comparable results as ..
- Pharmacokinetics and bioavailability of the bioflavonoid biochanin A: effects of quercetin and EGCG on biochanin A disposition in ratsYoung 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...
- Improving predictive modeling in pediatric drug development: pharmacokinetics, pharmacodynamics, and mechanistic modelingWilliam 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...
- Physiologically based approaches towards the prediction of pharmacokinetics: in vitro-in vivo extrapolationStefan S De Buck
Johnson and Johnson Pharmaceutical Research and Development, Division of Janssen Pharmaceutica N V, Discovery ADME Tox, Turnhoutseweg 30, B 2340 Beerse, Belgium
Expert Opin Drug Metab Toxicol 3:865-78. 2007..Finally, the ability of these prediction tools, when placed within a generic whole body physiologically based model of pharmacokinetics, to predict plasma concentration-time profiles is briefly discussed.
- An evaluation of the utility of physiologically based models of pharmacokinetics in early drug discoveryNeil Parrott
F Hoffmann La Roche AG, Pharmaceuticals Division, CH 4070 Bl, Switzerland
J Pharm Sci 94:2327-43. 2005Generic 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...
- Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populationsS 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...
- Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerationsImke 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...
- Review on pharmacokinetics and pharmacodynamics and the aging kidneyChristian Aymanns
Division of Nephrology, Department of Internal Medicine A, University of Greifswald, Greifswald, Germany
Clin J Am Soc Nephrol 5:314-27. 2010In people who are aged >65 years, pharmacokinetics are influenced more by the loss of kidney function than by the aging process of any other organ...
- The Simcyp population-based ADME simulatorMasoud 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...
- Facilitation of drug evaluation in children by population methods and modellingMichel 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. 2008The pharmacokinetics and pharmacodynamics of drugs are different in adult and paediatric populations, the latter being particularly heterogeneous...
- Theoretical versus empirical allometry: Facts behind theories and application to pharmacokineticsIftekhar 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 ..
- Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myelomaDouglas 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...
- Lumping in pharmacokineticsCeline 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...
- Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applicationsP Kannan
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
Clin Pharmacol Ther 86:368-77. 2009P-glycoprotein (P-gp), an efflux transporter, controls the pharmacokinetics of various compounds under physiological conditions...
- Applications of population pharmacokinetics in current drug labellingJ 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. 2007The 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.
- Prescribing medications in pediatrics: concerns regarding FDA approval and pharmacokineticsEmily 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.
- 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, ..
- Conditional weighted residuals (CWRES): a model diagnostic for the FOCE methodAndrew 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...
- Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinolRichard 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...
- The virtual laboratory approach to pharmacokinetics: design principles and conceptsWilhelm 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. 2006Modeling 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 ..
- Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugsIngolf 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...
- Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterionsTrudy 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...
- Essentials for starting a pediatric clinical study (1): Pharmacokinetics in childrenTsuyoshi 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...
- Parametric and nonparametric population methods: their comparative performance in analysing a clinical dataset and two Monte Carlo simulation studiesAida Bustad
Laboratory of Applied Pharmacokinetics, USC Keck School of Medicine, Los Angeles, California, USA
Clin Pharmacokinet 45:365-83. 2006..Nonparametric methods are better than parametric methods at analysing populations having unanticipated non-Gaussian or multimodal parameter distributions...
- 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....
- Applications of physiologically based absorption models in drug discovery and developmentNeil 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....
- The pharmacodynamics and pharmacokinetics of the oral direct thrombin inhibitor ximelagatran and its active metabolite melagatran: a mini-reviewDavid Gustafsson
Department of Cardiovascular Pharmacology, AstraZeneca R and D, Molndal, S 431 83 Molndal, Sweden
Thromb Res 109:S9-15. 2003..As a consequence of its favourable pharmacokinetic and pharmacodynamic properties, ximelagatran is currently undergoing full-scale clinical development for the prophylaxis and treatment of thromboembolic disorders...
- 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 practiceTrevor N Johnson
Simcyp Limited, Sheffield, UK
Paediatr Anaesth 21:291-301. 2011....
- Numerical simulation of local pharmacokinetics of a drug after intravascular delivery with an eluting stentDmitri V Sakharov
Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands
J Drug Target 10:507-13. 2002We 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 ..
- Pharmacokinetics and metabolism in early drug discoveryD 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...
- Physiologically-based pharmacokinetics in drug development and regulatory scienceMalcolm 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...
- Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjectsCharles 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...
- Methods of robust design of nonlinear models with an application to pharmacokineticsLee Kien Foo
School of Pharmacy, University of Otago, Dunedin, New Zealand
J Biopharm Stat 20:886-902. 2010..5th and 97.5th percentiles of the parameter space. The performance of the proposed optimality criteria is compared to two existing robust optimal design criteria...
- Population pharmacokinetics. A regulatory perspectiveH Sun
Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA
Clin Pharmacokinet 37:41-58. 1999..Certain preliminary information, such as the compartment model used in describing the pharmacokinetics of the drug, is required for a population pharmacokinetic study...
- ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactionsBéatrice 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...
- The process of knowledge discovery from large pharmacokinetic data setsE I Ette
Vertex Pharmaceuticals, Inc, 130 Waverly Street, Cambridge, MA 02139, USA
J Clin Pharmacol 41:25-34. 2001....
- Software for population pharmacokinetics and pharmacodynamicsL 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...
- Physiologically-based pharmacokinetic simulation modellingGeorge M Grass
LION Bioscience, 9880 Campus Point Drive, San Diego, CA 92121, USA
Adv Drug Deliv Rev 54:433-51. 2002....
- Information tools for exploratory data analysis in population pharmacokineticsO 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...
- Role of population pharmacokinetics in drug development. A pharmaceutical industry perspectiveE 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...
- Pharmacokinetics of high-dose chemotherapyY 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)...
- Food protein-stabilized nanoemulsions as potential delivery systems for poorly water-soluble drugs: preparation, in vitro characterization, and pharmacokinetics in ratsWei 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...
- Pharmacokinetics and physiologically-based pharmacokinetic modeling of nanoparticlesRaymond 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 ..
- The emerging importance of predictive ADME simulation in drug discoveryHarold E Selick
Camitro Corporation, 4040 Campbell Avenue, Menlo Park, CA94025, USA
Drug Discov Today 7:109-16. 2002..In the future we could see ADME properties designed-in from the first principles in drug design...
- Role of transport proteins in drug absorption, distribution and excretionA Ayrton
Mechanism and Extrapolation Technologies, DMPK, GlaxoSmithKline, Welwyn, UK
Xenobiotica 31:469-97. 2001..4. This review highlights the emerging role of transport proteins in ADE of drugs and suggests these need to be considered, in drug discovery and development, with respect to variability in drug disposition and response...
- Predicting pharmacokinetic food effects using biorelevant solubility media and physiologically based modellingHannah M Jones
Drug Metabolism and Pharmacokinetics, F Hoffmann-La Roche Ltd, Basel, Switzerland
Clin Pharmacokinet 45:1213-26. 2006..changes in gastric emptying time, gastric pH and/or intestinal fluid composition may have an impact on the pharmacokinetics of drugs...
- Introduction to in vitro estimation of metabolic stability and drug interactions of new chemical entities in drug discovery and developmentPaweł Baranczewski
Preclinical Development, Biovitrum AB, SE 112 76 Stockholm, Sweden
Pharmacol Rep 58:453-72. 2006..However, the quantitative output of the methods has to be improved. The aim of this review is to highlight the practical and theoretical basis of the in vitro metabolic methods and the recent progress in the development of these assays...
- Structure-ADME relationship: still a long way to go?Tingjun Hou
University of California at San Diego, Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, 9500 Gilman Drive, La Jolla, CA 92093 0359, USA
Expert Opin Drug Metab Toxicol 4:759-70. 2008..Theoretical models for predicting absorption, distribution, metabolism and excretion (ADME) properties play increasingly important roles in support of the drug development process...
- Assessment of dosing impact on intra-individual variability in estimation of parameters for basic indirect response modelsWojciech Krzyzanski
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
J Pharmacokinet Pharmacodyn 33:635-55. 2006..Highest variability was for IC (50) and SC (50) parameters. This study provides new insights into optimum study designs and recovery of parameters for basic IDR models...
- Chromatographic estimation of drug disposition properties by means of immobilized artificial membranes (IAM) and C18 columnsElisabet Lazaro
Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques 1, E 08028 Barcelona, Spain
J Med Chem 49:4861-70. 2006....
- truPK -- human pharmacokinetic models for quantitative ADME predictionKalyanasundaram Subramanian
Strand Genomics, 237 C V Raman Avenue, Sadashivanagar, Bangalore 560080, India
Expert Opin Drug Metab Toxicol 1:555-64. 2005..However, it has been difficult to locate reliable models for the prediction of human pharmacokinetics (PK) in silico Currently available methods for estimating ADME and toxicity properties, such as in vitro and ..
- Predictive ADME-Tox London, UK, 27 -- 28 April 2005Jennifer Fostel
US National Center for Toxicogenomics, National Institute for Environmental Health Sciences, Lockheed Martin Information Technology, Research Triangle Park, North Carolina, USA
Expert Opin Drug Metab Toxicol 1:565-70. 2005..In addition, collaboration to apply novel methods such as metabonomics profiling to withdrawn drugs may permit the identification of new safety biomarkers to prevent such costly failures...
- Pharmacokinetic simulation of biowaiver criteria: the effects of gastric emptying, dissolution, absorption and elimination ratesH Kortejärvi
Research and Development, Orion Pharma, P O Box 65, 02101 Espoo, Finland
Eur J Pharm Sci 30:155-66. 2007..but the factors related to the gastrointestinal tract and the dynamic nature of drug dissolution and systemic pharmacokinetics are not taken into account...
- Development and application of physiologically based pharmacokinetic-modeling tools to support drug discoveryChristian Lüpfert
Research Pharmacokinetics, Schering AG, Mullerstrasse 178, D 13342 Berlin
Chem Biodivers 2:1462-86. 2005..The stage is set for a wide penetration of PK modeling and simulations to form an intrinsic part of a project starting from lead discovery, to lead optimization and candidate selection, to preclinical profiling and clinical trials...
- Adapting therapy with repeated short-infusions to inter individual variability between patientsI D Rosca
Department of Polymer Chemistry, Polytechnic University, Bucharest, Romania
Eur J Drug Metab Pharmacokinet 32:87-99. 2007..5 of the drug, and the drug concentration at the peaks defined as a fraction of the first unchanged peak concentration...
- PK/DB: database for pharmacokinetic properties and predictive in silico ADME modelsTiago L Moda
Laboratory of Computational and Medicinal Chemistry, Center for Structural Molecular Biotechnology, Institute of Physics of São Carlos, University of Sao Paulo, São Carlos SP 13566 970, Brazil
Bioinformatics 24:2270-1. 2008....
- Modeling the drug transport in the anterior segment of the eyeRam Avtar
Department of Mathematics, Harcourt Butler Technological Institute, Kanpur 2008002, India
Eur J Pharm Sci 35:175-82. 2008....
- Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugsArik Dahan
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
J Control Release 129:1-10. 2008....
- From drug target to leads--sketching a physicochemical pathway for lead molecule design in silicoS A Shaikh
Department of Chemistry and Supercomputing Facility for Bioinformatics and Computational Biology, Indian Institute of Technology, Hauz Khas, New Delhi 110016, India
Curr Pharm Des 13:3454-70. 2007..The review thus summarizes recent advances and presents a viewpoint on improvements envisioned in the years to come for automated computer aided lead molecule discovery...
- EUFEPS conference on drug transporters at Copenhagen: integrative approaches in ADME researchDirk K F Meijer
Department of Pharmacokinetics and Drug Delivery, Groningen Institute for Drug Exploration (GUIDE, The Netherlands
Eur J Pharm Sci 26:130-43. 2005
- Intestinal first-pass metabolism: bridging the gap between in vitro and in vivoAleksandra Galetin
Curr Drug Metab 8:643-4. 2007
- N-in-1 dosing pharmacokinetics in drug discovery: experience, theoretical and practical considerationsKan He
Department of Pharmaceutical Candidate Optimization, Bristol Myers Squibb Company, PO Box 4000, Princeton, New Jersey 08543 4000, USA
J Pharm Sci 97:2568-80. 2008N-in-1 (or cassette) dosing pharmacokinetics (PK) has been used in drug discovery for rapid assessment of PK properties of new chemical entities...
- Advanced pharmacokinetic models based on organ clearance, circulatory, and fractal conceptsK Sandy Pang
Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, Canada M5S 3M2
AAPS J 9:E268-83. 2007Three advanced models of pharmacokinetics are described. In the first class are physiologically based pharmacokinetic models based on in vitro data on transport and metabolism...
- What is the true risk of a pharmacokinetic drug-drug interaction?Uwe Fuhr
Eur J Clin Pharmacol 63:897-9. 2007
- Prediction of human pharmacokinetics--gastrointestinal absorptionUrban Fagerholm
Clinical Pharmacology, AstraZeneca R and D Sodertalje, S 151 85 Södertälje, Sweden
J Pharm Pharmacol 59:905-16. 2007..Predictions of in-vivo dissolution should preferably be done from in-vitro dissolution data obtained using either real or validated simulated GI fluids...
- The current state of knowledge on age, sex, and their interactions on clinical pharmacologyJ B Schwartz
Jewish Home of San Francisco, University of California San Francisco, San Francisco, California, USA
Clin Pharmacol Ther 82:87-96. 2007Pharmacokinetic and pharmacodynamic changes occur with increasing age. Sex differences in pharmacokinetics and pharmacodynamics exist and persist at older age...
- Predicting human drug pharmacokinetics from in vitro permeability using an absorption-disposition modelKyle A Fliszar
Merck and Co, Inc Merck Manufacturing Division, West Point, Pennsylvania 19486, USA
J Pharm Sci 96:2161-70. 2007....
- Role of dosage regimen in controlling indirect pharmacodynamic responsesJ V Gobburu
Department of Pharmaceutics, State University of New York, Buffalo, NY 14260, USA
Adv Drug Deliv Rev 46:45-57. 2001....
- Importance of stereospecific bioanalytical monitoring in drug developmentJ Caldwell
Department of Pharmacology and Toxicology, St. Mary's Hospital Medical School, Paddington, London W2 1PG, UK
J Chromatogr A 719:3-13. 1996..The significance of the stereochemical aspects of pharmacokinetics and drug metabolism in both preclinical and clinical development is summarized and illustrated with reference ..
- A hybrid mixture discriminant analysis-random forest computational model for the prediction of volume of distribution of drugs in humanFranco Lombardo
Computational Chemistry and Scientific Computing Groups and Groton Non Clinical Statistics, Pfizer Global Research and Development, Groton Laboratories, Groton, Connecticut 06340, USA
J Med Chem 49:2262-7. 2006..The computational model described can predict human VD(ss) with an accuracy comparable to predictions requiring substantially greater effort and can be applied in place of animal experimentation...
- Quantitative evaluation of the function of small intestinal P-glycoprotein: comparative studies between in situ and in vitroYasuhisa Adachi
School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Pharm Res 20:1163-9. 2003..CONCLUSION: The in vitro transcellular transport across P-gp expressing monolayers may be used to predict the extent to which the intestinal absorption is affected by P-gp...
- In silico approaches for predicting ADME properties of drugsFumiyoshi Yamashita
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46 29 Yoshidashimoadachi cho, Sakyo ku, Kyoto 606 8501, Japan
Drug Metab Pharmacokinet 19:327-38. 2004..In addition, several methods of integrating ADME properties to predict pharmacokinetics at the organ or body level have been studied. In this article, we briefly summarize in silico ADME approaches.
- Organic chemistry in drug discoveryMalcolm MacCoss
Department of Basic Chemistry, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065, USA
Science 303:1810-3. 2004....
- [Clinical evaluation of therapeutic drug monitoring]Haruichi Kohno
Division of Pharmacy, National Hospital Organization Disaster Medical Center
Nippon Rinsho 62:351-5. 2004
- Biomarkers in drug discovery and development: from target identification through drug marketingWayne A Colburn
MDS Pharma Services, Phoenix, AZ, USA
J Clin Pharmacol 43:329-41. 2003....
- Estimating human drug oral absorption kinetics from Caco-2 permeability using an absorption-disposition model: model development and evaluation and derivation of analytical solutions for k(a) and F(a)Helen H Usansky
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA
J Pharmacol Exp Ther 314:391-9. 2005....
- The use of a physiologically based pharmacokinetic model to evaluate deconvolution measurements of systemic absorptionDavid G Levitt
Department of Physiology University of Minnesota, Minneapolis, MN 55455, USA
BMC Clin Pharmacol 3:1. 2003..The quantitative relation between the duration of the input and the accuracy of r is unknown. Although a large number of deconvolution procedures have been described, these routines are not available in a convenient software package...
- Computational prediction of oral drug absorption based on absorption rate constants in humansJohanna Linnankoski
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland
J Med Chem 49:3674-81. 2006..Thus, it was shown that, using a combination of only two computational molecular descriptors, it is possible to predict with good accuracy the K(a) value for a new drug candidate...
- Segmental intestinal transporters and metabolic enzymes on intestinal drug absorptionDebbie Tam
Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario, Canada M5S 2S2
Drug Metab Dispos 31:373-83. 2003..The simulations further showed that a descending metabolic intrinsic clearance yielded a lower F and an ascending segmental distribution of metabolic intrinsic clearance yielded a higher F...
- PHARMACODYNAMICS OF AGENTS FOR BLADDER CANCER THERAPYJESSIE AU; Fiscal Year: 2003This 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...
- Molecular mechanism of antiangiogenic properties of gold nanoparticlePriyabrata 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 ..
- Localized modulation of RPE P-gp/MRP activity for back-of-the-eye drug deliverySoumyajit 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...
- Azithromycin to prevent BPD in Ureaplasma-infected Preterms: Single Dose PK studyRose Viscardi; Fiscal Year: 2007..Currently, the pharmacokinetics, safety, and biologic effects of azithromycin in the preterm population are unknown...
- Drug Interactions and Bioavailability of CranberryJennifer 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...
- Multivalent Vaccine for Opiate AddictionPaul R Pentel; Fiscal Year: 2010..Vaccines which alter drug pharmacokinetics have shown substantial preclinical and preliminary clinical evidence of efficacy for nicotine and cocaine ..
- Movement-Responsive Cage for Simultaneous Pharmacology Studies in MiniPigsDouglas 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...
- K777 for treatment of Chagas Disease: IND-enabling Studies and IND SubmissionSHING 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...
- Investigating the Role of Adipocytes on Leukemia RelapseSTEVEN 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...
- Pilot Trial of Bumetanide for Neonatal SeizuresJANET 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...