Interindividual variability in inhibition and induction of cytochrome P450 enzymes.
Drug interactions have always been a major concern in medicine for clinicians and patients. Inhibition and induction of cytochrome P450 (CYP) enzymes are probably the most common causes for documented drug interactions. Today, many pharmaceutical companies are predicting potential interactions of new drug candidates. Can in vivo drug interactions be predicted accurately from in vitro metabolic studies? Should the prediction be qualitative or quantitative? Although some scientists believe that quantitative prediction of drug interactions is possible, others are less optimistic and believe that quantitative prediction would be very difficult. There are many factors that contribute to our inability to quantitatively predict drug interactions. One of the major complicating factors is the large interindividual variability in response to enzyme inhibition and induction. This review examines the sources that are responsible for the interindividual variability in inhibition and induction of cytochrome P450 enzymes.
Lin
J H
JH
Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Lu
A Y
AY
D000465:Algorithms; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System