A recent in vitro study has shown that paroxetine is a substrate of P-glycoprotein. However, there was no in vivo information indicating the involvement of P-glycoprotein on the pharmacokinetics of paroxetine. The aim of this study was to examine the effects of itraconazole, a P-glycoprotein inhibitor, on the pharmacokinetics of paroxetine. Two 6 day courses of either 200 mg itraconazole daily or placebo with at least a 4 week washout period were conducted. Thirteen volunteers took a single oral 20 mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 hours after the dosing. Compared with placebo, itraconazole treatment significantly increased the peak plasma concentration (Cmax) of paroxetine by 1.3 fold (6.7 ± 2.5 versus 9.0 ± 3.3 ng/mL, P < 0.05) and the area under the plasma concentration-time curve from zero to 48 hours [AUC (0-48)] of paroxetine by 1.5 fold (137 ± 73 versus 199 ± 91 ng*h/mL, P < 0.01). Although elimination half-life differed significantly (16.1 ± 3.4 versus 18.8 ± 5.9 hours, P < 0.05), the alteration was small (1.1 fold). The present study demonstrated that the bioavailability of paroxetine was increased by itraconazole, suggesting a possible involvement of P-glycoprotein in the pharmacokinetics of paroxetine.
From the *Department of Neuropsychiatry Hirosaki University School of Medicine, Hirosaki, Japan; †Department of Pharmacy, Hirosaki University Hospital, Hirosaki, Japan; and ‡MP-Technopharma Corporation, Fukuoka, Japan.
Received for publication August 2, 2006; accepted September 14, 2006.
This study was supported by a grant for priority research designated by the President of Hirosaki University, a Fund for Promotion of International Scientific Research, and a grant from the Hirosaki Research Institute for Neurosciences.
Correspondence: Department of Neuropsychiatry, Hirosaki University, School of Medicine, Hirosaki 036-8562, Japan (e-mail: firstname.lastname@example.org).