药品
体内
药物发现
药理学
药物开发
药物代谢
体外
医学
人口
药物相互作用
计算生物学
化学
生物
生物信息学
生物化学
遗传学
环境卫生
作者
Larry C. Wienkers,Timothy G. Heath
摘要
In vitro screening for drugs that inhibit cytochrome P450 enzymes is well established as a means for predicting potential metabolism-mediated drug interactions in vivo. Given that these predictions are based on enzyme kinetic parameters observed from in vitro experiments, the miscalculation of the inhibitory potency of a compound can lead to an inaccurate prediction of an in vivo drug interaction, potentially precluding a safe drug from advancing in development or allowing a potent inhibitor to 'slip' into the patient population. Here, we describe the principles underlying the generation of in vitro drug metabolism data and highlight commonly encountered uncertainties and sources of bias and error that can affect extrapolation of drug–drug interaction information to the clinical setting.
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