A Convenient Laboratory Experiment for Teaching the Fundamentals of Drug Metabolism

It is important that pharmacy students taking basic courses in pharmacology and toxicology are taught about function, regulation and multiplicity of drug metabolizing enzymes. We have developed an easy, reliably reproducible and relatively inexpensive laboratory work based on the different fluoresence properties of coumarin and its metabolites, 7-hydroxycoumarin and 7-O-glucuronide coumarin, to demonstrate the function of the enzymes involved in phases I and II of drug metabolism, their induction and inhibition in these phenomena. The work consists of three separate experiments: In the first part, nonfluorescent coumarin is hydroxylated to the blue light emitting 7-hydroxycoumarin by mouse liver microsomes. In the second part, this reaction is inhibited by pilocarpine but not by cimetidine, a well known inhibitor of several drug metabolizing enzymes. In the final part 7-hydroxycoumarin is conjugated 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.