Effect of repeated administration of eslicarbazepine acetate on the pharmacokinetics of simvastatin in healthy subjects

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Falcao, A (Author) Other; Pinto, R (Author) FMUP; Nunes, T (Author) Other; soares-da-silva, p (Author) FMUP

Journal

Title: Epilepsy Research

Vol. 106

Pages: 244-249

ISSN: 0920-1211

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 22 Citations

Other information

Authenticus ID: P-006-7HW

DOI: 10.1016/j.eplepsyres.2013.04.009

Abstract (EN): Objective: To investigate the effect of eslicarbazepine acetate (ESL) on the pharmacokinetics of simvastatin (SMV), a known CYP3A4 substrate, in healthy subjects. Methods: Single centre, two-way cross-over, randomized, open-label study in 24 healthy volunteers. The volunteers received an oral single-dose of SMV 80 mg on two occasions (once administered alone and once after treatment with an oral once-daily dose of 800 mg of ESL for 14 days), separated by a wash-out period of 3 weeks or more. The analysis of variance (ANOVA) was used to test for differences between Test (SMV under co-administration with ESL) and Reference (SMV administered alone) treatments for AUC(0-infinity), AUC(0-t) and C-max of SMV and SMV-acid. Results: Mean systemic exposure (AUC) measurements for both SMV and SMV-beta-hydroxyacid (SMV-acid) were up to 54% lower during ESL use. The Test/Reference geometric mean ratios (GMR) (90% CI) for the AUC(0-t) of SMV and SMV-acid were 46% (38%; 55%) and 49% (44%; 55%), respectively. Mean peak concentrations (C-max) of both SMV and SMV-acid were reduced by 60% and 41%, respectively, when SMV was administered with ESL. Conclusions: A significant effect of repeated ESL administration on the pharmacokinetics of SMV and its metabolite SMV-acid was observed. Therefore, dose adjustment of SMV may be required when used concomitantly with ESL, if a clinically significant change in lipids is noted.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6