Drug interactions of H-2-receptor antagonists involving cytochrome P450 (CYPs) enzymes: from the laboratory to the clinic

This paper reviews the main steps in the research of the interactions of H- 2,-receptor antagonist drugs with cytochrome P450 (CYP) enzymes. Cimetidine , ranitidine, and related compounds are used as examples. The results from in vitro studies are related to the observed clinically significant in vivo drug-drug and drug-chemical interactions. Uses of the in vitro results are discussed for the interpretation and possible prediction of drug-drug inte ractions, which may be important in developing new drugs. Other approach in the use of the in vitro data is to prevent undesirable and toxic actions o f drugs related to the catalytic activity of CYP enzymes. In the case of H- 2,-receptor antagonists, the inhibition of the metabolic reactions due to t he binding of the drugs with the enzymes was used to avoid side effects of co-administered drugs. The in vitro metabolic studies using recombinant hum an as well as animal CYP enzymes are now widely used as model systems for d esigning new drugs with improved therapeutic properties.