Human drug metabolism and the cytochromes P450: application and relevance of in vitro models

Journal of Clinical Pharmacology
K VenkatakrishnanD J Greenblatt


The cytochromes P450 (CYPs) constitute a superfamily of hemoprotein enzymes that are responsible for the biotransformation of numerous xenobiotics, including therapeutic agents. Studies of the biochemical and enzymatic properties of these enzymes and their molecular genetics and regulation of gene expression and activity have greatly enhanced our understanding of several aspects of clinical pharmacology such as pharmacokinetic variability, drug toxicity, and drug interactions. This review evaluates the major human hepatic drug-metabolizing CYP enzymes and their clinically relevant substrates, inhibitors, and inducers. Also discussed are the molecular bases and clinical implications of genetic polymorphisms that affect the CYPs. Much of the information on the specificity of substrates and inhibitors of the CYP enzymes is derived from in vitro studies using human liver microsomes and heterologously expressed CYP enzymes. These methods are discussed, and guidelines are provided for designing enzyme kinetic and reaction phenotyping studies using multiple approaches. The strengths, weaknesses, and discrepancies among the different approaches are considered using representative examples. The mathematical models used in predicting the...Continue Reading


Apr 1, 1978·Journal of Pharmacokinetics and Biopharmaceutics·K YamaokaT Uno
Oct 1, 1975·Clinical Pharmacology and Therapeutics·G R Wilkinson, D G Shand
Jun 1, 1990·British Journal of Clinical Pharmacology·D SesardicD S Davies
Jan 1, 1984·European Journal of Clinical Pharmacology·A Küpfer, R Preisig
Dec 1, 1984·Clinical Pharmacology and Therapeutics·P J WedlundR A Branch
Mar 1, 1995·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S J BaldwinR J Chenery
Jul 1, 1995·Clinical Pharmacology and Therapeutics·D Y GomezL Z Benet
Dec 1, 1994·Journal of Clinical Pharmacology·L L von MoltkeR I Shader
Oct 1, 1994·Journal of Pharmacokinetics and Biopharmaceutics·T M LuddenL B Sheiner
Jan 1, 1995·Methods in Enzymology·R B Silverman
Feb 22, 1994·Biochemistry·J A GoldsteinB I Ghanayem
Nov 1, 1993·Clinical Pharmacology and Therapeutics·D L KroetzR H Levy
Jul 1, 1993·Journal of Clinical Pharmacology·D J Greenblatt
Mar 24, 1993·Biochemical Pharmacology·K BrøsenS Loft
May 1, 1996·Clinical Pharmacology and Therapeutics·K E ThummelG R Wilkinson
Jul 15, 1996·Archives of Biochemistry and Biophysics·R E PearceA Parkinson
Jun 1, 1996·Pharmacogenetics·A K DalyU M Zanger
Jan 1, 1996·Fundamental & Clinical Pharmacology·J AhonenP J Neuvonen
May 1, 1996·Biopharmaceutics & Drug Disposition·T IwatsuboY Sugiyama
Oct 1, 1996·Journal of Clinical Psychopharmacology·A T Harvey, S H Preskorn
Nov 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S OnoT Satoh
Dec 1, 1996·Human & Experimental Toxicology·M Dickins, M K Bayliss

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