A CONVENIENT LABORATORY EXPERIMENT FOR TEACHING THE FUNDAMENTALS OF DRUG-METABOLISM

It is important that pharmacy students taking basic courses in pharmac ology and toxicology are taught about function, regulation and multipl icity of drug metabolizing enzymes. We have developed an easy, reliabl y reproducible and relatively inexpensive laboratory work based on the different fluoresence properties of coumarin and its metabolites, 7-h ydroxycoumarin and 7-O-glucuronide coumarin, to demonstrate the functi on of the enzymes involved in phases I and II of drug metabolism, thei r induction and inhibition in these phenomena. The work consists of th ree separate experiments: In the first part, nonfluorescent coumarin i s hydroxylated to the blue light emitting 7-hydroxycoumarin by mouse l iver microsomes. In the second part, this reaction is inhibited by pil ocarpine but not by cimetidine, a well known inhibitor of several drug metabolizing enzymes. In the final part 7-hydroxycoumarin is conjugat ed to nonfluorescent 7-O-glucuronide coumarin. The advantages of these experiments are that many students can be performing the experiments and learning drug metabolism simultaneously under the supervision of a single teacher.