Abstracts

Rationale: To determine steady-state plasma concentrations of retigabine (RTG), the first specific KCNQ channel opener antiepileptic drug, in patients with refractory partial-onset seizures when RTG administered as adjunctive therapy every 8 hrs. Methods: Blood samples obtained from patients enrolled in a long-term, open-label extension of placebo-controlled multicenter trial of RTG added to 1-3 AEDs. All patients on stable RTG doses adjusted to clinical need. Initial samples drawn after overnight fasting and before first daily RTG dose, then at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hrs postdose. Results: Plasma concentrations were analyzed in 15 patients (mean age, 39 yrs). Stabilized RTG dosages (mg/day): 600, n=2; 900, n=4; 1050, n=4; 1200, n=5. Mean peak plasma concentrations (µg/mL) were: 600 RTG, 0.94; 900 RTG, 1.01; 1050 RTG, 1.43; 1200 RTG, 1.85. Meantrough plasma concentrations (µg/mL) were: 600 RTG, 0.51; 900 RTG, 0.34; 1050 RTG, 0.74; 1200 RTG, 0.89. Mean average plasma concentrations (µg/mL) over the 8-hr dosing interval: 600 RTG, 0.68; 900 RTG, 0.66; 1050 RTG, 1.07; 1200 RTG, 1.34. Mean time to peak ranged from 1.0 hrs (600 and 900 RTG) to 2.3 hrs(1200 RTG). Conclusions: Steady-state RTG plasma concentrations increase with dosage over a range of 600 to 1200 mg/day. Funded by Valeant Pharmaceuticals International.