European Journal of Clinical Pharmacology

, Volume 32, Issue 2, pp 159–164 | Cite as

The influence of cimetidine versus ranitidine on doxepin pharmacokinetics

  • D. L. Sutherland
  • A. J. Remillard
  • K. R. Haight
  • M. A. Brown
  • L. Old


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.

Key words

doxepin cimetidine ranitidine pharmacokinetics biotransformation healthy volunteers 


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Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • D. L. Sutherland
    • 1
    • 2
  • A. J. Remillard
    • 2
  • K. R. Haight
    • 3
  • M. A. Brown
    • 2
    • 4
  • L. Old
    • 3
  1. 1.Saskatoon City HospitalSaskatoonCanada
  2. 2.College of PharmacyUniversity of SaskatchewanSaskatoonCanada
  3. 3.Department of Family Medicine, College of MedicineUniversity of SaskatchewanSaskatoonCanada
  4. 4.The Upjohn Company of CanadaDon MillsCanada

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