Cerebrospinal Fluid and Plasma Pharmacokinetics of Phenobarbital after Intravenous Administration to Patients with Status Epilepticus

The cerebrospinal fluid (CSF) and plasma pharmacokinetics of phenobarbital were studied after intravenous administration to 5 epileptic patients with convulsive status epilepticus and 6 seizure-free patients with newly diagnosed epilepsy. Phenobarbital (15 mg/kg) was infused at a rate of 100 mg/min. Plasma was collected prior to and throughout 24 hours after drug administration. The CSF samples were obtained by lumbar puncture 2 hours after the institution of phenobarbital infusion. Phenobarbital concentrations in plasma and the CSF were measured by reversed-phase liquid chromatography. The plasma values of pharmacokinetic variables of distribution and elimination did not differ between the groups. Slightly lower phenobarbital concentrations in the group of patients experiencing status epilepticus compared with seizure-free epileptic patients during the first hours after drug administration and the resultant elevated value of the rate constant of distribution (α) did not reach statistical significance, probably due to the small number of participants in the study. Phenobarbital concentrations were approximately 40% higher in the CSF of epileptic patients with status epilepticus compared with nonconvulsing subjects. The rate constant of phenobarbital distribution in the CSF (the ratio of the CSF concentration of the drug at time t1 and the area under the plasma concentration-time curve up to t1) in epileptic patients with status epilepticus exceeded that in seizure-free patients (0.29 ± 0.06h−1vs 0.19 ± 0.05h−1, p < 0.05). The study demonstrated statistically significantly higher phenobarbital concentrations and more rapid appearance of phenobarbital in the CSF of epileptic patients with status epilepticus compared with nonconvulsing patients with epilepsy. The alteration in the pharmacokinetics of phenobarbitone in patients experiencing status epilepticus reported here additionally supports the reported efficacy of intravenous phenobarbital in the treatment of this neurological disorder.