Effects of the P-glycoprotein inducer carbamazepine on fexofenadine pharmacokinetics.
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.
Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Satoshi
S
Yamada
Norio
N
Yasui-Furukori
Yumiko
Y
Akamine
Sunao
S
Kaneko
Tsukasa
T
Uno
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006634:Histamine H1 Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D006634:Histamine H1 Antagonists; D002220:Carbamazepine; D016593:Terfenadine; C093230:fexofenadine