The effects of cimetidine and ranitidine on the pharmacokinetics of cifenline

Twelve healthy subjects completed an open single dose study to evaluate the effect of co‐administration of cimetidine and ranitidine on the pharmacokinetics of cifenline. Each subject received a single 160 mg dose of cifenline alone, in combination with cimetidine (300 mg four times daily), and with ranitidine (150 mg twice daily). The H2‐receptor antagonists were given with breakfast 1 h prior to cifenline dosing and continuing for 48 h. Co‐administration of cimetidine significantly increased Cmax (27%) and AUC (44%) and prolonged the half‐life (30%) of cifenline. There were no differences in these parameters when ranitidine was co‐administered with cifenline. The results of this study suggest that cimetidine, but not ranitidine, lowers the clearance of cifenline by inhibition of hepatic oxidative metabolism.