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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