In vitro screening of drug metabolism during drug development: can we trust the predictions?

Abstract

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.

Keywords::

• CYP
• cytochrome P450
• drug metabolism