Cytochromes P450: decision-making tools for personalized therapeutics.
The responses of patients to standard drug regimens vary widely, with dose responses ranging from subtherapeutic to toxic. The primary goal of individualized medicine is the optimization of drug therapy, which involves the selection of appropriate drugs, dosages and drug combinations, and the minimization of toxic side effects. The cytochrome P450 (CYP) enzymes mediate the oxidative biotransformation of most drugs, and are important determinants of the duration of drug action. CYPs exhibit a large number of allelic variants that may encode defective enzymes or no enzyme at all. The expression and function of these enzymes are also influenced (induced or inhibited) by non-genetic factors. Patients with diminished CYP capacity may require lower than normal doses of certain drugs, whereas those with an increased metabolic capacity may need higher than normal doses in order to achieve fill efficacy. This review focuses on the recent developments in the field of CYP pharmacogenetics that include characterization of the substrate- and inhibitor-specificity of CYP variant enzymes, and the increasing evidence that polygenic factors influence the design of personalized drug regimens.
Murray
Michael
M
Pharmacogenomics and Drug Development Group, Faculty of Pharmacy, University of Sydney, NSW2006, Australia. michaelm@pharm.usyd.edu.au
Petrovic
Nenad
N
D000483:Alleles; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D004358:Drug Therapy; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D010641:Phenotype
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System