The influence of cimetidine versus ranitidine on doxepin pharmacokinetics.
The effect of cimetidine and ranitidine on doxepin pharmacokinetics was studied in 6 healthy volunteers. Each subject completed 3 study phases: Treatment A, 9 consecutive doses of 50 mg doxepin (once daily); Treatment B, same as Treatment A but co-administration of cimetidine 600 mg b.i.d. starting after the sixth doxepin dose and continuing until approximately 2 days following discontinuation of doxepin administration; Treatment C, identical to Treatment B but with ranitidine 150 mg b.i.d. instead of cimetidine. Unlike ranitidine, cimetidine co-administration resulted in a significant increase in steady state plasma levels of doxepin (4.7, 9.0 and 4.5 ng/ml during Treatments A, B and C respectively) but not desmethyldoxepin (4.1, 4.6 and 4.2 ng/ml during Treatments A, B and C respectively). Elimination half-lives of doxepin and desmethyldoxepin were prolonged by cimetidine co-administration (19.6 and 26.2 h respectively), but remained unchanged during the ranitidine treatment phase (13.3 and 18.4 h) as compared to the control phase i.e. Treatment A (13.2 and 19.0 h). These results show that cimetidine, unlike ranitidine, significantly inhibits the biotransformation of doxepin. This data has clinical implications when the co-administration of tricylic antidepressants and H2-receptor antagonists are indicated.
D000293:Adolescent; D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D004316:Doxepin / Q000031:analogs & derivatives / Q000097:blood*; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*
D004316:Doxepin; D002927:Cimetidine; D011899:Ranitidine; C028701:desmethyldoxepin