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Titolo:
CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline
Autore:
Alfaro, CL; Lam, YWF; Simpson, J; Ereshefsky, L;
Indirizzi:
Univ Texas, Hlth Sci Ctr, Div Pharmacotherapy, Dept Pharmacol, San Antonio, Univ Texas San Antonio TX USA 78284 therapy, Dept Pharmacol, San Antonio, Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA Univ Texas San Antonio TX USA 78284 , Dept Med, San Antonio, TX 78284 USA Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA Univ Texas San Antonio TX USA 78284 t Psychiat, San Antonio, TX 78284 USA Univ Texas, Coll Pharm, Austin, TX 78712 USA Univ Texas Austin TX USA 78712 iv Texas, Coll Pharm, Austin, TX 78712 USA Alamo Mental Hlth Grp, San Antonio, TX USA Alamo Mental Hlth Grp San Antonio TX USA l Hlth Grp, San Antonio, TX USA NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892 H, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 2, volume: 19, anno: 1999,
pagine: 155 - 163
SICI:
0271-0749(199904)19:2<155:CSOEMA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
SEROTONIN REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; HUMAN-LIVER-MICROSOMES; DRUG-INTERACTIONS; PLASMA-CONCENTRATIONS; POOR METABOLIZERS; MAJOR DEPRESSION; HEALTHY-SUBJECTS; IN-VITRO; DESIPRAMINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Ereshefsky, L Univurlxas, Hlth Sci Ctr, Div Pharmacotherapy, Dept Pharmacol, 7703 Floyd C Univ Texas 7703 Floyd Curl Dr San Antonio TX USA 78284 oyd C
Citazione:
C.L. Alfaro et al., "CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline", J CL PSYCH, 19(2), 1999, pp. 155-163

Abstract

The aim of this study was to evaluate the CYP2D6 inhibitory effects of four selective cerotonin reuptake inhibitors (SSRIs). Thirty-one healthy subjects were phenotyped as extensive metabolizers using the dextromethorphan/dextrorphan (DM/DX) urinary ratio as a marker for CYP2D6 activity before and after 8 days of administration of fluoxetine 60 mg (loading dose strategy),fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg in a parallel-group design. Statistical analysis was performed on log-transformed DM/DX ratios because of variability within and between treatment groups. DM/DX ratios before (DM/DXBL) and after (DM/DXSSRI) were compared within and between the four SSRI groups. DM/DXBL ratios were not significantly different between the four SSRI treatment groups. Comparing within groups, significant differences between DM/DXBL and DM/DXBL were found for the fluoxetine (p < 0.001; ratio values, 0.020 vs. 0.364) and paroxetine (p = 0.0005, ratio values0.028 vs. 1.085) but not for the fluvoxamine or sertraline groups. Comparing between groups, significant differences in DM/DXSSRI ratios were found for fluoxetine versus sertraline (p = 0.0019, DM/DX = 0.364 vs. 0.057), fluoxetine versus fluvoxamine (p < 0.0001, DM/DX = 0.364 vs. 0.019), paroxetineversus sertraline (p = 0.0026, DM/DX = 1.085 vs. 0.057), and paroxetine versus fluvoxamine (p < 0.0001, DM/DX = 1.085 vs. 0.019). No significant differences were noted between the two potent CYP2D6 inhibitors, fluoxetine andparoxetine, or the two weakest inhibitors, fluvoxamine and sertraline. Five subjects in dhe fluoxetine and four subjects in the paroxetine groups changed to poor metabolizer phenotype (DM/DX greater than or equal to 0.3) after treatment, Although CYP2D6 inhibitory effects of fluvoxamine and sertraline did not yield significant differences from baseline, some subjects exhibited DM/DX ratio increases of 150 to 200%. One paroxetine-treated subject did not exhibit any CYP2D6 inhibition. SSRI dose and plasma concentration may be correlated with the extent of CYP2D6 inhibition and should be furtherinvestigated.

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Documento generato il 19/01/20 alle ore 20:08:06