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Titolo:
Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers
Autore:
Harvey, AT; Preskorn, SH;
Indirizzi:
Inst Psychiat Res, Wichita, KS 67214 USA Inst Psychiat Res Wichita KS USA67214 sychiat Res, Wichita, KS 67214 USA Univ Kansas, Sch Med, Dept Psychiat, Wichita, KS 67214 USA Univ Kansas Wichita KS USA 67214 ed, Dept Psychiat, Wichita, KS 67214 USA
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 2, volume: 21, anno: 2001,
pagine: 161 - 166
SICI:
0271-0749(200104)21:2<161:FPAEOC>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; SEROTONIN REUPTAKE INHIBITORS; CLINICAL PHARMACOKINETICS; DEPRESSED-PATIENTS; PAROXETINE; HYDROXYLATION; PHARMACOLOGY; METABOLITES; DESIPRAMINE; POPULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Harvey, AT Inst Psychiat Res, 1100 N St Francis,Suite 200, Wichita, KS 67214 USA Inst Psychiat Res 1100 N St Francis,Suite 200 Wichita KS USA 67214
Citazione:
A.T. Harvey e S.H. Preskorn, "Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers", J CL PSYCH, 21(2), 2001, pp. 161-166

Abstract

The objective of this study was to assess in both young and elderly volunteers the pharmacokinetics of fluoxetine and norfluoxetine and effects on cytochrome P450 (CYP) 2C19. Male volunteers aged 18 to 40 years (N = 14) or older than 65 years (N = 16) received fluoxetine 20 mg/day for 6 weeks and fluoxetine 40 mg/day for an additional 6 weeks. Blood was drawn over a 24-hour period after the initial dose and after 6 weeks and 12 weeks to determine AUC(0-24), C-max, and t(max); weekly to evaluate predose levels (C-0); and over a 3-week period after discontinuation to evaluate washout (t(1/2)). Mephenytoin was used to assess CYP2C19 activity before and after 6 weeks and 12 weeks of fluoxetine. Fluoxetine AUC(0-24), C-0, and C-max did not differ in young and elderly subjects. The norfluoxetine C-0 was 22% lower in elderly subjects (p < .05), with comparable decreases in AUC(0-24) and C-max. In the elderly volunteers, the t(1/2) for fluoxetine was 25% longer (5.0 vs. 4.0 days) and for norfluoxetine was 33% longer (20 vs. 15 days), although variability and sample size precluded statistical significance. Fluoxetine dosing inhibited CYP2C19 activity in both age groups, increasing the (S)-to (R)-mephenytoin ratio 3- to 4-fold (p < .01). The half-lives of fluoxetine and norfluoxetine at 40 mg/day were longer than commonly reported in the literature and may be longer in elderly subjects. Fluoxetine substantially inhibited the metabolism of the CYP2C19 substrate (S)-mephenytoin.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/02/20 alle ore 17:14:14