Evidence for a pharmacokinetic interaction between eslicarbazepine and rosuvastatin: Potential effects on xenobiotic transporters

•Rosuvastatin exposure was decreased (∼40%) with concomitant steady-state ESL.•The decreased rosuvastatin exposure may result from reduced oral bioavailability.•The reduced rosuvastatin exposure is unlikely due to increased oxidative metabolism.•When rosuvastatin is used with ESL, rosuvastatin dose adjustment may be necessary.•In healthy subjects, ESL 1200 mg QD was generally well tolerated.

IntroductionPatients with partial-onset seizures and comorbid cardiovascular disease may concomitantly receive eslicarbazepine acetate (ESL), an antiepileptic drug, and rosuvastatin, an HMG-CoA reductase inhibitor. This study evaluated the effect of multiple-dose ESL on the pharmacokinetic (PK) parameters of a single dose of rosuvastatin in healthy subjects.MethodsThis was a Phase I, single-center, fixed-sequence, open-label study. Healthy subjects received two treatments, in sequence. Treatment A: a single 40 mg oral dose of rosuvastatin on Day 1, followed by a washout period (Days 1-4); treatment B: titration of ESL (400-800 mg once daily) on Days 5-18, followed by ESL 1200 mg once daily on Days 19-35, with a single dose of rosuvastatin (40 mg) on Day 32. Subjects then entered a 2-week follow-up period. Plasma concentrations of rosuvastatin were quantified for PK analyses. Safety and tolerability were assessed throughout the study.ResultsThirty-three healthy subjects were enrolled and 30 completed the study. Mean rosuvastatin (standard deviation) t1/2 was similar when rosuvastatin was used concomitantly with ESL and when it was used alone (26.5 [16.3] h, and 22.4 [9.5] h, respectively). The geometric least squares mean ratios (90% confidence intervals) of rosuvastatin exposure levels between rosuvastatin used concomitantly with ESL and rosuvastatin used alone were as follows: Cmax, 64.0% (55.9-73.3%); AUC(0-∞), 63.0% (57.1-69.4%); and AUC(0-last), 60.9% (55.2-67.1%). Concomitant use of ESL and rosuvastatin was generally well tolerated.ConclusionsRosuvastatin exposure was 36-39% lower with steady-state administration of ESL, potentially due to reduced oral bioavailability of rosuvastatin. Consequently, when rosuvastatin is used with ESL, a rosuvastatin dose adjustment may be necessary if a clinically significant change in lipids is noted.