Safety and pharmacokinetics of intravenous add-on levetiracetam in status epilepticus

Objective: To evaluate safety of intravenous levetiracetam added to the standard therapeutic regimen in adults with status epilepticus. and to assess a population pharmacokinetic model for intravenous levetiracetam in patients with status epilepticus. Design: Prospective, single-centre, single-arm, open-label study. Methods: In 12 adults presenting with status epilepticus, levetiracetam 2500 mg intravenous was added as soon as possible to standardized protocol. During 24 hours of follow-up, patients were observed for any clinically relevant side effects. A population pharmacokinetic model was developed by iterative two-stage Bayesian analysis and compared to pharmacokinetic data of healthy volunteers. Results: 11 patients with a median age of 60 years were included in the per protocol analysis. 5 were diagnosed as having generalised-convulsive status epilepticus, 5 as partial-convulsive status epilepticus and 1 as a non-convulsive status epilepticus. Blood samples for pharmacokinetic analysis were available for 10 patients. No serious side effects could be directly related to the intravenous administration of levetiracetam. A two-compartment population pharmacokinetic model gave the best description of intravenous levetiracetam pharmacokinetics. Mean (SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) l/kg, and total body clearance: 0.048 (0.0147) l·h-1·kg-1. Mean maximum plasma concentration was 85 (19) mg/l. No large deviations from the known pharmacokinetic of intravenous levetiracetam in healthy volunteers were observed. Conclusion: The addition of intravenous levetiracetam to the standard regimen for controlling status epilepticus seems feasible and safe. Pharmacokinetic data of intravenous levetiracetam in patients with status epilepticus correspond to earlier values derived from healthy volunteers, confirming a two-compartment population model