Time-dependence of clobazam and N-demethylclobazam kinetics in healthy volunteers.
The pharmacokinetic behavior of clobazam and its main metabolite, norclobazam, was investigated in healthy subjects after single dose administration, repeated dose administration (28 days) and discontinuation of the treatment (15-day follow-up). The aim of the study was to confirm the time-invariance of the clobazam and/or norclobazam kinetics, in order to evaluate the predictive value of the single dose parameters for chronic administration of this drug. The comparisons of parameters after single dose and for 15 days following cessation of chronic administration, experimental and simulated plasma level-time courses, experimental and calculated steady-state minimum plasma concentrations, and half-life values at apparent and deep elimination phase, indicate a time-invariant behavior of clobazam, whereas the norclobazam pharmacokinetics appeared to be clearly time-dependent. The clinical importance of this difference cannot be adequately assessed until more is known about the contribution of norclobazam to the overall effect of the parent drug.
D000328:Adult; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000097:blood*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000097:blood* / Q000378:metabolism; D001711:Biotransformation; D000078306:Clobazam; D006207:Half-Life; D006801:Humans; D007700:Kinetics
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D001569:Benzodiazepines; D000078306:Clobazam; C024581:N-desmethylclobazam