Pelkonen Olavi, Turpeinen Miia, Uusitalo Jouko, Rautio Arja, Raunio Hannu
Department of Pharmacology and Toxicology, University of Oulu, Box 5000, FIN-90014 Oulu, Finland.
Basic Clin Pharmacol Toxicol. 2005 Mar;96(3):167-75. doi: 10.1111/j.1742-7843.2005.pto960305.x.
Drug metabolism profoundly affects drug action, because almost all drugs are metabolised in the body and thus their concentrations and elimination rates are dependent on metabolic activity. Drug metabolism contributes substantially to interindividual differences in drug response and is also often involved in drug interactions, resulting in either therapeutic failure or adverse effects. Knowledge about the metabolism of a new chemical entity and its affinity to drug-metabolising enzymes helps in the drug development process by providing important information for the selection of a lead compound from among a number of substances pharmacologically equally effective in their therapeutic response. In drug development protocols, metabolism characteristics should be assessed very early during the development process. This has been made possible by the advances made especially in analytical capabilities and in in vitro technologies that are employed to predict in vivo metabolite profile, pharmacokinetic parameters and drug-drug interaction potential.
药物代谢对药物作用有深远影响，因为几乎所有药物都会在体内代谢，因此它们的浓度和消除速率取决于代谢活性。药物代谢在很大程度上导致了个体对药物反应的差异，并且常常参与药物相互作用，从而导致治疗失败或产生不良反应。了解新化学实体的代谢及其对药物代谢酶的亲和力，有助于在药物开发过程中从许多在治疗反应上具有同等药理效力的物质中选择先导化合物，从而提供重要信息。在药物开发方案中，应在开发过程的早期就评估代谢特征。特别是在分析能力和用于预测体内代谢物谱、药代动力学参数和药物相互作用潜力的体外技术方面取得的进展，使得这一点成为可能。
