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Titolo:
Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan,a CYP2D6 probe
Autore:
Amchin, J; Ereshefsky, L; Zarycranski, W; Taylor, K; Albano, D; Klockowski, PM;
Indirizzi:
Wyeth Ayerst Labs, Philadelphia, PA USA Wyeth Ayerst Labs Philadelphia PAUSA Ayerst Labs, Philadelphia, PA USA Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA Univ Pittsburgh Pittsburgh PA USA Med, Dept Psychiat, Pittsburgh, PA USA Univ Texas, Hlth Sci Ctr, Pharmacotherapy Div, San Antonio, TX USA Univ Texas San Antonio TX USA , Pharmacotherapy Div, San Antonio, TX USA
Titolo Testata:
JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 4, volume: 41, anno: 2001,
pagine: 443 - 451
SICI:
0091-2700(200104)41:4<443:EOVVFO>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VITRO; CYTOCHROME-P450 SYSTEM; DRUG-INTERACTIONS; PHARMACOKINETICS; INHIBITION; ANTIDEPRESSANTS; HYDROXYLATION; FLUVOXAMINE; PHENOTYPE; QUINIDINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Amchin, J Wyeth Ayerst Labs, 240 N Radnor Chester Rd, St Davids, PA 19087 USA Wyeth Ayerst Labs 240 N Radnor Chester Rd St Davids PA USA 19087
Citazione:
J. Amchin et al., "Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan,a CYP2D6 probe", J CLIN PHAR, 41(4), 2001, pp. 443-451

Abstract

Two antidepressants, venlafaxine and fluoxetine, were evaluated in vivo for their effect on cytochrome P450 2D6 (CYP2D6) activity, measured by the ratio of dextromethorphan, a sensitive CYP2D6 marker, to its metabolite dextrorphan (i.e., DM:DT) excreted in urine after DM coadministration. Twenty-eight healthy extensive metabolizers of CYP2D6 received either venlafaxine (37.5 mg bid for 7 days, then 75 mg bid until Day 28) or fluoxetine (20 mg daily for 28 days); 26 completed the study. Plasma concentrations of both drugs and their active metabolites were determined. DM:DTs were evaluated at baseline (Day 0), on Days 7 and 28 of dosing, and 2 weeks after drug discontinuation (Day 42). Steady-state drug and metabolite levels were achieved inboth groups by Day 28. Mean DM:DTs for venlafaxine and fluoxetine differedstatistically significantly (p < 0.001) on Days 7 28, and 42. Comparisons of DM:DT as a percentage of baseline values showed that DM:DT increased 1.2-fold for venlafaxine and 9.1-fold for fluoxetine on Day 7 (p < 0.001) and increased 2.1-fold for venlafaxine and 17.1-fold for fluoxetine on Day 28 (p < 0.001). Inhibition of CYP2D6 metabolism persisted for 2 weeks after discontinuation of fluoxetine, unlike the case with venlafaxine. These in vivoresults confirm in vitro data demonstrating significantly weaker inhibition of CYP2D6 with venlafaxine than with fluoxetine. This suggests that clinically significant interactions involving CYP2D6 inhibition could occur between fluoxetine and drugs metabolized by CYP2D6 bur may be less likely to occur with venlafaxine. <(c)> 2001 the American College of Clinical Pharmacology.

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Documento generato il 29/03/20 alle ore 01:51:01