EFFECTS OF ERYTHROMYCIN, CLARITHROMYCIN AND ROKITAMYCIN ON NIFEDIPINEMETABOLISM IN RATS

The effects of erythromycin, clarithromycin and rokitamycin on the met abolism of nifedipine were studied in vitro and in situ. Erythromycin, clarithromycin or rokitamycin added to nifedipine did not inhibit the formation of metabolite, M-l, of nifedipine, whereas pretreatment wit h erythromycin or clarithromycin significantly (p < 0.05) inhibited it s formation, Only erythromycin significantly (p < 0.05) inhibited the formation of M-2 from M-l, These observations agreed with the results obtained using an in situ rat intestinal loop technique, As assessed b y the concentrations of nifedipine and M-2 in jugular and portal vein blood, the inhibition of nifedipine metabolism by erythromycin was gre ater after multiple doses than after a single dose. Moreover, our resu lts suggest that rokitamycin is a less potent inhibitor of nifedipine metabolism.