Doxepin-cimetidine interaction

Increased doxepin bioavailability during cimetidine treatment

Darrell R. Abernethy, Elizabeth L. Todd

Research output: Contribution to journalArticle

Abstract

The influence of concurrent cimetidine administration on the disposition of doxepin was evaluated in 10 healthy volunteers. Each subject ingested 100 mg of doxepin on two different occasions, once while otherwise drug free and once while receiving cimetidine, 300 mg every 6 hours. Doxepin absorptive parameters—time to peak doxepin plasma concentration (2.3, control, vs. 2.4 hours during cimetidine coadministration) and peak concentration achieved (43.3. vs. 55.5 ng/ml)—were not changed during cimetidine administration. Likewise, doxepin elimination halflife was similar in the control state (12.5 hours) and during cimetidine administration (13.2 hours).However, doxepin area under the plasma concentration-time curve (AUC) was increased during concurrent cimetidine administration (533 vs. 695 ng/ml • hour; p <0.05), resulting in a trend toward decreased doxepin oral clearance (4404 vs. 3278 ml/min; 0.05 <p <0.1). Relative bioavailabilty during concurrent cimetidine treatment was 123% of that during the control trial. Desmethyldoxepin AUC was no different between trials (478, control, vs. 433 ng/ml • hour during cimetidine ingestion). Plasma protein binding of doxepin was similar between trials (percent unbound; 10.5, control, vs. 11.2%) and therefore did not influence calculated AUC. These data indicate that doxepin relative bioavailability is increased during concurrent cimetidine administration and suggest that doxepin hepatic extraction is impaired by cimetidine after oral administration. During chronic doxepin therapy, addition of cimetidine to a therapeutic regimen may result in increased doxepin plasma concentrations.

Original languageEnglish (US)
Pages (from-to)8-12
Number of pages5
JournalJournal of Clinical Psychopharmacology
Volume6
Issue number1
StatePublished - 1986
Externally publishedYes

Fingerprint

Doxepin
Cimetidine
Biological Availability
Therapeutics
Area Under Curve
Protein Binding
Oral Administration
Half-Life

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Psychiatry and Mental health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Doxepin-cimetidine interaction : Increased doxepin bioavailability during cimetidine treatment. / Abernethy, Darrell R.; Todd, Elizabeth L.

In: Journal of Clinical Psychopharmacology, Vol. 6, No. 1, 1986, p. 8-12.

Research output: Contribution to journalArticle

@article{3e782c169cdc4bfdb0fc50274e947959,
title = "Doxepin-cimetidine interaction: Increased doxepin bioavailability during cimetidine treatment",
abstract = "The influence of concurrent cimetidine administration on the disposition of doxepin was evaluated in 10 healthy volunteers. Each subject ingested 100 mg of doxepin on two different occasions, once while otherwise drug free and once while receiving cimetidine, 300 mg every 6 hours. Doxepin absorptive parameters—time to peak doxepin plasma concentration (2.3, control, vs. 2.4 hours during cimetidine coadministration) and peak concentration achieved (43.3. vs. 55.5 ng/ml)—were not changed during cimetidine administration. Likewise, doxepin elimination halflife was similar in the control state (12.5 hours) and during cimetidine administration (13.2 hours).However, doxepin area under the plasma concentration-time curve (AUC) was increased during concurrent cimetidine administration (533 vs. 695 ng/ml • hour; p <0.05), resulting in a trend toward decreased doxepin oral clearance (4404 vs. 3278 ml/min; 0.05",
author = "Abernethy, {Darrell R.} and Todd, {Elizabeth L.}",
year = "1986",
language = "English (US)",
volume = "6",
pages = "8--12",
journal = "Journal of Clinical Psychopharmacology",
issn = "0271-0749",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Doxepin-cimetidine interaction

T2 - Increased doxepin bioavailability during cimetidine treatment

AU - Abernethy, Darrell R.

AU - Todd, Elizabeth L.

PY - 1986

Y1 - 1986

N2 - The influence of concurrent cimetidine administration on the disposition of doxepin was evaluated in 10 healthy volunteers. Each subject ingested 100 mg of doxepin on two different occasions, once while otherwise drug free and once while receiving cimetidine, 300 mg every 6 hours. Doxepin absorptive parameters—time to peak doxepin plasma concentration (2.3, control, vs. 2.4 hours during cimetidine coadministration) and peak concentration achieved (43.3. vs. 55.5 ng/ml)—were not changed during cimetidine administration. Likewise, doxepin elimination halflife was similar in the control state (12.5 hours) and during cimetidine administration (13.2 hours).However, doxepin area under the plasma concentration-time curve (AUC) was increased during concurrent cimetidine administration (533 vs. 695 ng/ml • hour; p <0.05), resulting in a trend toward decreased doxepin oral clearance (4404 vs. 3278 ml/min; 0.05

AB - The influence of concurrent cimetidine administration on the disposition of doxepin was evaluated in 10 healthy volunteers. Each subject ingested 100 mg of doxepin on two different occasions, once while otherwise drug free and once while receiving cimetidine, 300 mg every 6 hours. Doxepin absorptive parameters—time to peak doxepin plasma concentration (2.3, control, vs. 2.4 hours during cimetidine coadministration) and peak concentration achieved (43.3. vs. 55.5 ng/ml)—were not changed during cimetidine administration. Likewise, doxepin elimination halflife was similar in the control state (12.5 hours) and during cimetidine administration (13.2 hours).However, doxepin area under the plasma concentration-time curve (AUC) was increased during concurrent cimetidine administration (533 vs. 695 ng/ml • hour; p <0.05), resulting in a trend toward decreased doxepin oral clearance (4404 vs. 3278 ml/min; 0.05

UR - http://www.scopus.com/inward/record.url?scp=0022626328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022626328&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 8

EP - 12

JO - Journal of Clinical Psychopharmacology

JF - Journal of Clinical Psychopharmacology

SN - 0271-0749

IS - 1

ER -