Effects of the P-glycoprotein Inducer Carbamazepine on Fexofenadine Pharmacokinetics

Abstract

The aim of this study was to evaluate the possible effects of carbamazepine, a P-glycoprotein inducer, on fexofenadine pharmacokinetics. Twelve healthy Japanese volunteers (nine males and three females) were enrolled in this study after giving written informed consent. This randomized open-label study consisted of two phases (control and 7-day treatment) with a 2-week washout period. In the control phase, volunteers received 60 mg fexofenadine hydrochloride after an overnight fast. In the treatment phase, carbamazepine was dosed 100 mg three times daily (for a total daily dose of 300 mg) for 7 days, and on Day 7, a single 60-mg dose of fexofenadine was coadministered with a 100-mg dose of carbamazepine. The plasma concentrations and urinary excretion of fexofenadine were measured for 24 hours after dosing. Carbamazepine pretreatment significantly altered fexofenadine pharmacokinetics, decreasing the mean (+/- standard deviation) peak plasma concentration from 176.6 (+/- 82.1) ng/mL to 103.2 (+/- 33.6) ng/mL (P < 0.01) and the area under the plasma concentration-time curve from 1058.4 (+/- 528.7) ng/h/mL to 604.8 (+/- 255.9) ng/h/mL (P < 0.01) without changing the elimination half-life. Relatively, carbamazepine significantly reduced the amount of fexofenadine excreted into the urine from 8.1 (+/- 2.1) mg to 4.5 (+/- 1.4) mg (P < 0.001), although the renal clearance of fexofenadine remained constant between the two study phases. Thus, this study indicates that carbamazepine significantly decreases fexofenadine plasma concentrations, probably as a result of P-glycoprotein induction in the small intestine. Carbamazepine treatment, therefore, is of moderate clinical significance for patients receiving fexofenadine.