POSSIBLE ROLE OF THE INTESTINAL P-450 ENZYME-SYSTEM IN A CYCLOSPORINECLARITHROMYCIN INTERACTION

Clarithromycin is a macrolide antibiotic similar in structure to eryth romycin, but suggested to have fewer drug interactions. Although a pha rmacokinetic interaction between clarithromycin and cyclosporine was r ecently reported, its magnitude and mechanism have not been explored. A 43-year-old renal transplant recipient receiving cyclosporine was tr eated with clarithromycin because of pneumonia. A cyclosporine pharmac okinetic study was performed 8 days after the initiation of the clarit hromycin and 14 days after stopping the drug. Clarithromycin coadminis tration caused an approximately 2-fold increase in the area under the whole blood concentration versus time curve of cyclosporine. The oral clearance of cyclosporine was halved by clarithromycin, but the termin al elimination rate constant decreased only 15% and mean residence tim e 20%. These observations suggest that clarithromycin inhibits not onl y the hepatic metabolism but also the intestinal metabolism of cyclosp orine. Caution is advised when administering the two drugs concurrentl y, and additional studies are necessary to elucidate the mechanism of this interaction.