Effect of the frequently used antiepileptic drugs carbamazepine, gabapentin, and pregabalin on the pharmacokinetics of edoxaban and other oral factor xa inhibitors in healthy volunteers.

ABSTRACT:

Purpose

Pregabalin, gabapentin, and carbamazepine, a potent inducer of cytochrome P450 (CYP) 3A4 and P-glycoprotein, are frequently used antiepileptic drugs that are often administered together with factor Xa inhibitors (FXaI). We aimed to investigate whether potentially clinically relevant drug-drug interactions occur with these combinations.

Methods

In an open-label fixed-sequence trial in 36 healthy volunteers, we evaluated the pharmacokinetics of 60 mg edoxaban and of a microdosed FXaI cocktail (25 µg apixaban, 50 µg edoxaban, and 25 µg rivaroxaban) before and during treatment with carbamazepine (12 evaluable volunteers, individually dosed to therapeutic concentrations), gabapentin (11 volunteers, titrated to 3 × 400 mg/d), and pregabalin (12 volunteers, titrated to 2 ×

SUBMITTER: Lenard A 

PROVIDER: S-EPMC12022901 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature