Summary
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Pinder RM, Brogden RN, Speight TM, Avery GS (1977) Doxepin up-to-date: A review of its pharmacological properties and therapeutic efficacy with particular reference to depression. Drugs 13: 161–218
Kimura Y, Kume M, Kageyama K (1972) Absorption, distribution and metabolism of doxepin hydrochloride. Pharmacometrics 6: 955–971
Faulkner RD, Pitts WM, Lee CS, Lewis WA, Fann WE (1983) Multiple dose doxepin kinetics in depressed patients. Clin Pharmacol Ther 34: 509–515
Virtanen R, Scheinim M, Iisalo E (1980) Single dose pharmacokinetics of doxepin in healthy volunteers. Acta Pharmacol Toxicol 47: 371–376
Ziegler VE, Biggs JT, Wylie LT, Rosen ST, Hawf DJ, Coryell UH (1978) Doxepin kinetics. Clin Pharmacol Ther 23: 573–579
Bell JA, Gower AJ, Martin LE, Mills EN, Smith WP (1981) Interactions of H2-receptor antagonists with drug-metabolizing enzymes. Biochem Soc Trans 9: 113–114
Gerber MC, Tejwani GA, Gerber N, Bianchine JR (1985) Drug interactions with cimetidine: An update. Pharmacol Ther 27: 353–370
Rendic S, Kajfez F, Ruf HH (1983) Characterization of cimetidine, ranitidine and related structures — interaction with cytochrome P-450. Drug Metab Dispos 11: 137–142
Somogyi A, Gugler R (1982) Drug interactions with cimetidine. Clin Pharmacokinet 7: 23–41
Kirch W, Hoensch H, Janisch HD (1984) Interactions and non-interactions with ranitidine. Clin Pharmacokinet 9: 493–510
Brown MA, Haight KR, McKay G (1985) Cimetidine-doxepin interaction. A case report and clinical investigation. J Clin Psychopharmacol 5: 245–247
Berardi RR, Caplan NB (1983) Agents with tricyclic structures for treating peptic ulcer disease. Clin Pharm 2: 425–431
Mangla JC, Pereira MP (1982) Tricyclic antidepressants in the treatment of peptic ulcer disease. Arch Intern Med 142: 273–275
Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York
Abernethy DR, Todd EL (1986) Doxepin-cimetidine interaction: Increased doxepin bioavailability during cimetidine treatment. J Clin Psychopharmacol 6: 8–12
Hobbs DC (1969) Distribution and metabolism of doxepin. Biochem Pharmacol 18: 1941–1954
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sutherland, D.L., Remillard, A.J., Haight, K.R. et al. The influence of cimetidine versus ranitidine on doxepin pharmacokinetics. Eur J Clin Pharmacol 32, 159–164 (1987). https://doi.org/10.1007/BF00542189
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00542189