The Role of Metabolish Studies in Drug Safety Evaluation

Abstract

There is a general recognition now of the importance of drug metabolism studies in the process of drug development and the drug regulatory authorities certainly expect to see the results of such studies. However, it is not always appreciated just how closely such studies must be integrated with many other aspects of drug development. In normal practice, metabolism studies are carried out by the metabolism scientist working closely with the pharmacologist, the pharmacist, the toxicologist and the clinician; these interactions can, and should play a key role in determining the strategy of such studies.

Let us first consider the time—scale which applies to metabolism studies in safety evaluation. In Fig. 1, the left hand column shows the major steps in the evaluation of the desirable biological effects of the drug. After identification of promising activity in animal models and completion of satisfactory initial toxicity studies, come the first studies in man, either in normal volunteers or in patients, followed by further studies (phase II) to establish the efficacy of the compound, phase III studies involving wide—scale comparative trials, and finally hopefully the launch of the drug. On the right hand side of the Figure, the drug may first enter a toxicity screen designed