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.