Pelkonen Olavi, Raunio Hannu
University of Oulu, Department of Pharmacology and Toxicology, Box 5000, FIN-90014 Oulu, Finland.
Expert Opin Drug Metab Toxicol. 2005 Jun;1(1):49-59. doi: 10.1517/17425255.1.1.49.
Due to the importance of drug metabolism for drug action, side effects, interactions and interindividual differences, in vitro assays of drug metabolism are widely employed during drug development. Validation of the in vitro systems is still in a rather elementary stage, but some tentative conclusions about their performance for predicting various important in vivo characteristics of drugs can be attempted. So far, prediction of drug-drug interactions on the basis of in vitro screens has been advanced to a relatively reliable level. Prediction of other important characteristics, such as metabolic stability and consequent half-life and dosage schedule, or induction potential, is less reliable. Although metabolite profiles and participating enzymes are predicted quite accurately with advanced analytical techniques, an important problem here is the lack of reliable methods to detect reactive metabolites or products, which may be of significance regarding toxicity.
由于药物代谢对药物作用、副作用、相互作用及个体差异具有重要意义，药物代谢的体外试验在药物研发过程中被广泛应用。体外系统的验证仍处于相当初级的阶段，但可以尝试就其预测药物各种重要体内特性的性能得出一些初步结论。到目前为止，基于体外筛选预测药物 - 药物相互作用已发展到相对可靠的水平。预测其他重要特性，如代谢稳定性以及随之而来的半衰期和给药方案，或诱导潜力，则不太可靠。尽管利用先进的分析技术能够相当准确地预测代谢物谱和参与的酶，但这里一个重要的问题是缺乏可靠的方法来检测可能与毒性相关的反应性代谢物或产物。
