CEREBROSPINAL-FLUID AND PLASMA PHARMACOKINETICS OF PHENOBARBITAL AFTER INTRAVENOUS ADMINISTRATION TO PATIENTS WITH STATUS EPILEPTICUS

The cerebrospinal fluid (CSF) and plasma pharmacokinetics of phenobarb ital were studied after intravenous administration to 5 epileptic pati ents with convulsive status epilepticus and 6 seizure-free patients wi th newly diagnosed epilepsy. Phenobarbital (15 mg/kg) was infused at a rate of 100 mg/min. Plasma was collected prior to and throughout 24 h ours after drug administration. The CSF samples were obtained by lumba r puncture 2 hours after the institution of phenobarbital infusion. Ph enobarbital concentrations in plasma and the CSF were measured by reve rsed-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 pa tients experiencing status epilepticus compared with seizure-free epil eptic patients during the first hours after drug administration and th e resultant elevated value of the rate constant of distribution (a) di d not reach statistical significance, probably due to the small number of participants in the study. Phenobarbital concentrations were appro ximately 40% higher in the CSF of epileptic patients with status epile pticus compared with nonconvulsing subjects. The rate constant of phen obarbital distribution in the CSF (the ratio of the CSF concentration of the drug at time tl and the area under the plasma concentration-tim e curve up to tl) in epileptic patients with status epilepticus exceed ed that in seizure-free patients (0.29 +/- 0.06h(-1) vs 0.19 +/- 0.05h (-1), p < 0.05). The study demonstrated statistically significantly hi gher phenobarbital concentrations and more rapid appearance of phenoba rbital in the CSF of epileptic patients with status epilepticus compar ed with nonconvulsing patients with epilepsy. The alteration in the ph armacokinetics of phenobarbitone in patients experiencing status epile pticus reported here additionally supports the reported efficacy of in travenous phenobarbital in the treatment of this neurological disorder .