Lin J H, Lu A Y
Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Annu Rev Pharmacol Toxicol. 2001;41:535-67. doi: 10.1146/annurev.pharmtox.41.1.535.
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.
药物相互作用一直是临床医生和患者在医学领域主要关注的问题。细胞色素P450（CYP）酶的抑制和诱导可能是已记录的药物相互作用最常见的原因。如今，许多制药公司都在预测新药候选物的潜在相互作用。能否从体外代谢研究准确预测体内药物相互作用？这种预测应该是定性的还是定量的？尽管一些科学家认为药物相互作用的定量预测是可能的，但另一些人则不太乐观，认为定量预测会非常困难。有许多因素导致我们无法对药物相互作用进行定量预测。一个主要的复杂因素是个体对酶抑制和诱导反应的巨大差异。本综述探讨了导致细胞色素P450酶抑制和诱导个体差异的来源。
