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7319299 
Journal Article 
Review 
Physiologically-based pharmacokinetics in drug development and regulatory science 
Rowland, M; Peck, C; Tucker, G 
2011 
Yes 
Annual Review of Pharmacology and Toxicology
ISSN: 0362-1642
EISSN: 1545-4304 
Annual Review of Pharmacology and Toxicology 
51 
45-73 
English 
20854171 
WOS:000287956600003 
The application of physiologically-based pharmacokinetic (PBPK) modeling is coming of age in drug development and regulation, reflecting significant advances over the past 10 years in the predictability of key pharmacokinetic (PK) parameters from human in vitro data and in the availability of dedicated software platforms and associated databases. Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation. The value of this capability in selecting and designing appropriate clinical studies, its implications for resource-sparing techniques, and a more holistic view of the application of PK across the preclinical/clinical divide are considered. 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. 
drug regulation; industrial; mechanistic; modeling; simulation; alfentanil; astemizole; caffeine; cerivastatin; cimetidine; cisapride; clopidogrel; cytochrome P450; cytochrome P450 2C9; diclofenac; dofetilide; drug metabolizing enzyme; etiracetam; glucuronosyltransferase; levacetylmethadol; lidocaine; metoprolol; mibefradil; midazolam; nifedipine; omeprazole; paroxetine; quinidine; sildenafil; tamoxifen; terfenadine; theophylline; warfarin; age; allometry; area under the curve; article; binding affinity; breast cancer; drug absorption; drug clearance; drug concentration; drug design; drug development; drug distribution; drug elimination; drug excretion; drug formulation; drug half life; drug interaction; drug legislation; drug metabolism; drug receptor binding; drug research; enzyme inhibition; gene expression; genetic polymorphism; genetic variability; heart reinfarction; human; in vitro study; inflammation; intermethod comparison; kidney disease; liver cell; liver clearance; liver dysfunction; liver microsome; Monte Carlo method; nonhuman; pharmacogenetics; pharmacokinetics; physiologically based pharmacokinetics; priority journal; QT prolongation; rhabdomyolysis; torsade des pointes; Animals; Clinical Trials as Topic; Computer Simulation; Drug and Narcotic Control; Drug Approval; Drug Design; Drug Interactions; Humans; Individualized Medicine; Models, Biological; Pharmaceutical Preparations; Pharmacokinetics