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.
Massarella
J W
JW
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Defeo
T M
TM
Liguori
J
J
Passe
S
S
Aogaichi
K
K
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000493:pharmacokinetics*; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D002927:Cimetidine; D011899:Ranitidine; C032151:cifenline