Disease relevance of Norclobazam

• Clobazam and N-desmethylclobazam serum concentrations in endstage renal failure and hemodialysis [1].

High impact information on Norclobazam

• Clobazam itself has a half-life of 18 hours, but that of the principal metabolite, N-desmethylclobazam, is about 50 hours [2].
• STP inhibited N-demethylation of CLB to N-desmethylclobazam (NCLB) mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with K(i) = 1.59 +/- 0.07 and 0.516 +/- 0.065 microM and IC(50) = 1.58 microM [95% confidence interval (CI95%) = 1.20-2.08] and 3.29 microM (CI95% = 1.87-5.79), respectively [3].
• Interactions with other drugs metabolized by these P450s can occur; moreover, the CYP2C19 genetic polymorphism could be responsible for interindividual variations of plasma concentrations of N-desmethylclobazam and thus for occurrence of adverse events [4].
• Pharmacokinetics of N-desmethylclobazam in healthy volunteers and patients with epilepsy [5].
• The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam [6].

Biological context of Norclobazam

• 1. The pharmacokinetics of clobazam and its biotransformation product N-desmethylclobazam were investigated after single and multiple doses in normal subjects [7].
• Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses [8].
• A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam [9].
• To our knowledge, this is one of few reports describing tissue concentrations of ethosuximide collected at autopsy and the first report of clobazam/desmethylclobazam tissue distribution in man [10].

Anatomical context of Norclobazam

• The concentrations of both clobazam and N-desmethylclobazam were higher in serum than in cerebrospinal fluid (CSF) [11].

Associations of Norclobazam with other chemical compounds

• A method is described for the simultaneous determination of clobazam, its active metabolite N-desmethylclobazam, and clonazepam in plasma by high performance liquid chromatography [12].

Analytical, diagnostic and therapeutic context of Norclobazam

• Micro-determination of clobazam and N-desmethylclobazam in plasma or serum by electron-capture gas chromatography [13].
• Liquid chromatography determination of clobazam and its major metabolite N-desmethylclobazam in human plasma [14].
• Analysis of clobazam and its active metabolite norclobazam in plasma and serum using HPLC/DAD [15].

References