Title:Clinical Pharmacokinetics of Retigabine/Ezogabine
Volume: 8
Issue: 4
Author(s): Debra J. Tompson and Christopher S. Crean
Affiliation:
Keywords:
Antiepileptic drug, biopharmaceutical properties, epilepsy, ezogabine, pharmacokinetics, retigabine.
Abstract: Background: Retigabine is an antiepileptic drug that reduces neuronal excitability by enhancing potassium
channel activity.
Methods: This manuscript summarizes the pharmacokinetic and biopharmaceutical properties of retigabine collated from
published and unpublished in vitro and clinical phase I–III studies in healthy volunteers or patients with partial-onset
seizures.
Results: Retigabine is rapidly absorbed with a median time to Cmax of 0.5–2.0 hours. Thereafter, plasma concentrations
decline in a mono-exponential manner, with a median half-life of 6–8 hours. The absolute oral bioavailability of
retigabine is ~60%. Retigabine is metabolized extensively by N-acetylation and subsequent N-glucuronidation. In vitro
and in vivo studies have shown that the drug-interaction potential of retigabine is low. The pharmacokinetics of retigabine
are linear over the dose range 200–400mg three times daily (tid), with ~ 35–50% between-subject variability. Systemic
exposure was not affected by a high fat meal, but Cmax was, ~14% and ~38% higher in the fed versus fasted state for the
200 and 400mg tablets, respectively. Retigabine drug-related material is primarily eliminated renally with unchanged
retigabine accounting for ~36%. Retigabine plasma clearance decreased as severity of renal or hepatic impairment
increased. Systemic exposure to retigabine is unaffected by gender when normalized for body weight. In elderly patients,
retigabine systemic exposure was higher, and half-life was longer than in younger patients.
Conclusions: Retigabine should be administered tid without regard to food. No adjustments required for gender, race, or
genetic/polymorphisms. Dosage adjustments are recommended in elderly patients and those with moderate and severe
renal or moderate hepatic impairment.
