Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. High metabolic lability usually leads to poor bioavailability and high clearance. Formation of active or toxic metabolites will have an impact on the pharmacological and toxicological outcomes. There is also potential for drug-drug interactions with coadministered drugs due to inhibition and/or induction of drug metabolism pathways. Hence, optimization of the metabolic liability and drug-drug interaction potential of the new chemical entities are some of the most important steps during the drug discovery process. The rate and site(s) of metabolism of new chemical entities by drug metabolizing enzymes are amenable to modulation by appropriate structural changes. Similarly, the potential for drug-drug interactions can also be minimized by appropriate structural modifications to the drug candidate. However, the optimization of the metabolic stability and drug-drug interaction potential during drug discovery stage has been largely by empirical methods and by trial and error. Recently, a lot of effort has been applied to develop predictive methods to aid the optimization process during drug discovery and development. This article reviews the role of drug metabolism in drug discovery and development.

中文翻译：

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药物代谢在药物发现和开发中的作用。

宿主生物的代谢是药物药代动力学特征的最重要决定因素之一。高代谢不稳定性通常导致较差的生物利用度和高清除率。活性或有毒代谢产物的形成将对药理和毒理学结果产生影响。由于药物代谢途径的抑制和/或诱导，与共同给药的药物也存在药物相互作用的潜力。因此，在药物发现过程中，优化新化学实体的代谢作用和药物与药物之间的相互作用潜力是一些最重要的步骤。新的化学实体通过药物代谢酶代谢的速率和部位可以通过适当的结构变化进行调节。同样，药物相互作用的潜力也可以通过对候选药物进行适当的结构修饰而最小化。然而，在药物发现阶段，代谢稳定性和药物-药物相互作用潜能的最优化主要是通过经验方法和反复试验。近来，已经进行了很多努力来开发预测方法，以辅助药物发现和开发过程中的优化过程。本文回顾了药物代谢在药物发现和开发中的作用。在开发预测方法以帮助药物发现和开发过程中的优化过程方面已进行了大量努力。本文回顾了药物代谢在药物发现和开发中的作用。在开发预测方法以帮助药物发现和开发过程中的优化过程方面已进行了大量努力。本文回顾了药物代谢在药物发现和开发中的作用。