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Current Clinical Pharmacology

Editor-in-Chief

ISSN (Print): 1574-8847
ISSN (Online): 2212-3938

Effect of Hemodialysis on Pharmacokinetics of Ezogabine/Retigabine and its N-Acetyl Metabolite in Patients with End Stage Renal Disease

Author(s): Debra J. Tompson, Mauro Buraglio, Jonathan Bullman, Christopher S. Crean and Kirsty Rayner

Volume 9 , Issue 4 , 2014

Page: [319 - 325] Pages: 7

DOI: 10.2174/157488470904141105142635

Price: $65

Abstract

Ezogabine (EZG)/retigabine (RTG) and its metabolites are mainly eliminated renally. This Phase 1 study assessed the effect of hemodialysis on the pharmacokinetics of EZG/RTG and its N-acetyl metabolite (NAMR) in patients with end-stage renal disease; tolerability of EZG/RTG was a secondary endpoint. Patients (N=8) received EZG/RTG 100 mg orally 4 hours before (Period 1) or following (Period 2) dialysis. Blood (both periods) and dialysate (Period 1) samples were taken up to 68 hours post dose. Tolerability was assessed throughout both periods. The area under the concentration– time curve (0–68 hours) for EZG/RTG was 33% lower (geometric mean ratio [90% confidence interval]: 0.67 [0.61, 0.73]) on dialysis versus off dialysis and 43% lower for NAMR (0.57 [0.53, 0.62]). Median (range) reductions in plasma concentrations from dialysis start to end were 52% (17–59%) for EZG/RTG and 51% (27–72%) for NAMR. EZG/RTG 100 mg was generally tolerated.

Keywords: End-stage renal disease, ezogabine, hemodialysis, pharmacokinetics, retigabine, tolerability.


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