Carbamazepine differentially affects the pharmacokinetics of fexofenadine enantiomers

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • We have shown that P‐glycoprotein (P‐gp) inhibitors such as itraconazole and verapamil significantly increase the plasma concentrations of fexofenadine enantiomers, and their effects are greater for (S)‐fexofenadine compared with the (R)‐enantiomer. These mechanisms are likely to be due to inhibition of intestinal P‐gp because the t 1/2 and CL R were constant during the study, and suggest that intestinal P‐gp plays an important role in the pharmacokinetics of fexofenadine enantiomers. To date, there is no information whether the P‐gp inducer carbamazepine affects the pharmacokinetics of either fexofenadine enantiomer. WHAT THIS STUDY ADDS • This study indicates that the stereoselectivity of fexofenadine pharmacokinetics may be influenced by carbamazepine primarily due to the induction of intestinal P‐gp, and this effect may be greater for (S)‐fexofenadine compared with (R)‐fexofenadine. However, since the inductive effect of carbamazepine did not eliminate the difference between the pharmacokinetics of the fexofenadine enantiomers, it is likely that other transporters, including OATP2B1 and MRP2, also contribute to the stereoselective pharmacokinetics of fexofenadine. AIM This aim of this study was to characterize the impact of the P‐glycoprotein (P‐gp) inducer, carbamazepine, on fexofenadine enantiomer pharmacokinetics. METHODS Twelve healthy volunteers initially received a 60 mg dose of fexofenadine alone. Subsequently, a 100 mg dose of carbamazepine was administered three times daily (300 mg day −1 ), and on day 7, fexofenadine was co‐administered. RESULTS Carbamazepine significantly decreased the area under the plasma concentration–time curve and the amount excreted into the urine of (S)‐ and (R)‐fexofenadine. The P‐gp inducer showed a greater effect on the pharmacokinetic parameters of (S)‐fexofenadine. CONCLUSION This study indicates that carbamazepine may alter the pharmacokinetics of fexofenadine enantiomers.