Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men

Background and objectives: Fluvoxamine, a selective serotonin reuptake inhi bitor, is known to inhibit several hepatic cytochrome P450 (CYP) isozymes, in particular CYP1A2. Mexiletine is mainly catalyzed by CYP2D6 and partiall y catalyzed by CYP1A2, Our objective was to study the potential pharmacokin etic interaction between fluvoxamine and mexiletine. Methods: A randomized crossover design with two phases was used. A 7-day wa shout period separated the two treatment conditions. In the one phase, 6 he althy Japanese men received an oral dose of 200 mg of mexiletine alone (stu dy 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) a nd fluvoxamine concomitantly (study 2). The concentrations of mexiletine we re measured with HPLC. Results: The area under the concentration-time curve and serum peak concent ration of mexiletine in study 2 were significantly increased compared with those in study 1 (10.4 +/- 4.85 versus 6.70 +/- 3.21 mug (.) h/mL, P = .006 and 0.623 +/- 0.133 versus 0.536 +/- 0.164 mug/mL, P = .008, respectively) . Conclusion: The effect of fluvoxamine on the mexiletine disposition is comp aratively large, and when mexiletine and fluvoxamine are coadministered car eful monitoring of mexiletine is needed.