Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy

Levetiracetam (LEV) has antiepileptogenic effects in animals and is a candidate for prevention of epilepsy after traumatic brain injury. Pharmacokinetics of LEV in TBI patients was unknown. We report pharmacokinetics of TBI subjects >= 6 years with high PTE risk treated with LEV 55 mg/kg/day orally, nasogastrically or intravenously for 30 days starting <= 8 h after injury in a phase II safety and pharmacokinetic study. Forty-one subjects (26 adults and 15 children) were randomized to PK studies on treatment days 3 and 30. Thirty-six out of forty-one randomized subjects underwent PK study on treatment day 3, and 24/41 subjects underwent PK study on day 30. On day 3, mean T-max was 2.2 h, C-max was 60.2 mu g/ml and AUC was 403.7 mu g/h/ml. T-max was longer in the elderly than in children and non-elderly adults (5.96 h vs. 1.5 h and 1.8 h; p=0.0001). AUC was non-significantly lower in children compared with adults and the elderly (317.4 mu g/h/ml vs. 461.4 mu g/h/ml and 450.2 mu g/h/ml; p=0.08). C-max trended higher in i.v.-versus tablet-or n.g.-treated subjects (78.4 mu g/ml vs. 59 mu g/ml and 48.2 mu g/ml; p=0.07). AUC of n.g. and i.v. administrations was 79% and 88% of AUC of oral administration. There were no significant PK differences between days 3 and 30. Treatment of TBI patients with high PTE risk with 55 mg/kg/day LEV, a dose with antiepileptogenic effect in animals, results in plasma LEV levels comparable to those in animal studies. (C) 2012 Elsevier Inc. All rights reserved.