Serum and cerebrospinal fluid concentration of clobazam and N-desmethylclobazam

Twelve adult neurological patients undergoing lumbar puncture for diagnostic purposes received acute or repeated doses of the 1,5-benzodiazepine clobazam 20-40 mg/day. In one patient, additional ventricle cerebrospinal fluid samples were collected in the course of the diagnostic procedure and the respective concentrations of clobazam and N-desmethylclobazam were determined. The serum and lumbar cerebrospinal fluid concentrations of clobazam and its main metabolite N-desmethylclobazam were compared. The concentrations of both clobazam and N-desmethylclobazam were higher in serum than in cerebrospinal fluid (CSF). Clobazam and N-desmethylclobazam showed similar increase and decline in the ventricle CSF of one patient. This result differed from the pharmacokinetics of clobazam and its main metabolite in the blood which is characterized by a slower increase and a more prolonged elimination of N-desmethylclobazam, as opposed to the parent compound.