Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans
Autore:
Lessard, E; Yessine, MA; Hamelin, BA; Gauvin, C; Labbe, L; OHara, G; LeBlanc, J; Turgeon, J;
Indirizzi:
Laval Hosp, Quebec Heart Inst, Quebec City, PQ, Canada Laval Hosp Quebec City PQ Canada bec Heart Inst, Quebec City, PQ, Canada Univ Laval, Fac Pharm, Quebec City, PQ, Canada Univ Laval Quebec City PQ Canada val, Fac Pharm, Quebec City, PQ, Canada Univ Laval, Fac Med, Quebec City, PQ, Canada Univ Laval Quebec City PQ Canada Laval, Fac Med, Quebec City, PQ, Canada Robert Giffard Hosp Ctr, Dept Pharmacol, Quebec City, PQ, Canada Robert Giffard Hosp Ctr Quebec City PQ Canada l, Quebec City, PQ, Canada
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 2, volume: 21, anno: 2001,
pagine: 175 - 184
SICI:
0271-0749(200104)21:2<175:DATDOV>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; LIVER-MICROSOMES; IN-VITRO; HUMAN-PLASMA; HEALTHY-MEN; OXIDATION; PHARMACOKINETICS; SPARTEINE; RAT; ANTIDEPRESSANT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Turgeon, J Univ Montreal, Fac Pharm, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada Univ Montreal CP 6128,Succursale Ctr Ville Montreal PQ Canada H3C 3J7
Citazione:
E. Lessard et al., "Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans", J CL PSYCH, 21(2), 2001, pp. 175-184

Abstract

CYP2D6 is the major enzyme involved in the metabolism of venlafaxine. Subjects with a low CYP2D6 activity have increased plasma concentrations of venlafaxine that may predispose them to cardiovascular side effects. In vitro and in vivo studies showed that diphenhydramine, a nonprescription antihistamine, can inhibit CYP2D6 activity. Therefore, the authors investigated in this study a potential drug interaction between diphenhydramine and venlafaxine. Fifteen male volunteers, nine with the extensive metabolizer (EM) andsix with the poor metabolizer (PM) phenotype of CYP2D6, received venlafaxine hydrochloride 18.75 mg orally every 12 hours for 48 hours on two occasions (1 week apart): once alone and once during the concomitant administration of diphenhydramine hydrochloride (50 mg every 12 hours). Blood and urine samples were collected for 12 hours under steady-state conditions. In EMs, diphenhydramine decreased venlafaxine oral clearance from 104 +/- 60 L/hr to 43 +/- 23 L/hr (mean +/- SD; p < 0.05) without any effect on renal clearance (4 <plus/minus> 1 L/hr during venlafaxine alone and 4 +/- 2 L/hr duringvenlafaxine plus diphenhydramine). In PMs, coadministration of diphenhydramine did not cause significant changes in oral clearance and partial metabolic clearances of venlafaxine to its various metabolites. Diphenhydramine disposition was only slightly affected by genetically determined low CYP2D6 activity or concomitant administration of venlafaxine. In conclusion, diphenhydramine, at therapeutic doses, inhibits CYP2D6-mediated metabolism of venlafaxine in humans. Clinically significant interactions could be encountered during the concomitant administration of diphenhydramine and other antidepressant or antipsychotic drugs that are substrates of CYP2D6.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 09:23:27