Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men.
Clin Pharmacol Ther
; 69(3): 104-7, 2001 Mar.
Article
en En
| MEDLINE
| ID: mdl-11240973
ABSTRACT
BACKGROUND AND OBJECTIVES:
Fluvoxamine, a selective serotonin reuptake inhibitor, is known to inhibit several hepatic cytochrome P450 (CYP) isozymes, in particular CYP1A2. Mexiletine is mainly catalyzed by CYP2D6 and partially catalyzed by CYP1A2. Our objective was to study the potential pharmacokinetic interaction between fluvoxamine and mexiletine.METHODS:
A randomized crossover design with two phases was used. A 7-day washout period separated the two treatment conditions. In the one phase, 6 healthy Japanese men received an oral dose of 200 mg of mexiletine alone (study 1); in the other phase, the men received fluvoxamine (50 mg twice a day) for 7 days, and on the eighth day they received oral mexiletine (200 mg) and fluvoxamine concomitantly (study 2). The concentrations of mexiletine were measured with HPLC.RESULTS:
The area under the concentration-time curve and serum peak concentration of mexiletine in study 2 were significantly increased compared with those in study 1 (10.4 +/- 4.85 versus 6.70 +/- 3.21 microg x h/mL, P =.006 and 0.623 +/- 0.133 versus 0.536 +/- 0.164 microg/mL, P =.008, respectively).CONCLUSION:
The effect of fluvoxamine on the mexiletine disposition is comparatively large, and when mexiletine and fluvoxamine are coadministered careful monitoring of mexiletine is needed.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fluvoxamina
/
Inhibidores Selectivos de la Recaptación de Serotonina
/
Mexiletine
/
Antiarrítmicos
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
2001
Tipo del documento:
Article
País de afiliación:
Japón