Pharmacokinetic Drug Interactions Between Clobazam and Drugs Metabolized by Cytochrome P450 Isoenzymes

Abstract

These findings suggest no clinically meaningful drug-drug interactions between clobazam and drugs metabolized by CYP3A4, CYP2C19, CYP1A2, or CYP2C9. Concomitant use of drugs metabolized by CYP2D6 may require dosage adjustment. Clobazam may be administered safely as adjunctive therapy in patients with Lennox-Gastaut syndrome, without meaningful changes in clobazam pharmacokinetics that would require dosage adjustment.

Independent Predictors of Delay in Emergence From General Anesthesia

“…On the other hand, clobazam is a weak inducer of CYP3A4 and has the potential to induce UGT1A1, but it does not have a significant induction or inhibition effect on CYPs at clinically meaningful concentrations in vitro. 28 Clonazepam has also been shown to have no induction effect on CYP1A2 and CYP3A4 in vitro, 29,30 and is reportedly clinically safe in drug interactions. 30 Although phenobarbital induces CYP2B2, CYP2B6, CYP2C, CYP3A, and UGT1A-like mRNAs, [11][12][13] a direct effect on propofol metabolism has never been examined.…”

Therapeutic Drug Monitoring of Clobazam and Its Metabolite—Impact of Age and Comedication on Pharmacokinetic Variability

“…However, authors of 2 recent studies concluded that there were no clinically relevant drug-drug interactions with selected AEDs, based on a pharmacokinetic modeling approach with grouped comedication. 30,31 However, the methodology of studies on interactions between CLB and other drugs varies to an extensive degree. Important factors to consider include sampling time, drugs included in the comparison group, and CYP2C19 polymorphisms in the studied ethnic groups.…”

Comprehensive overview: efficacy, tolerability, and cost-effectiveness of clobazam in Lennox–Gastaut syndrome

“…The drug’s bioavailability is high at approximately 87%, and peak concentrations are achieved at median time of 1 hour (range: 1–4 hours) 34,35. Metabolism occurs mainly via the cytochrome P450 (CYP450) enzymes.…”

“…Metabolism occurs mainly via the cytochrome P450 (CYP450) enzymes. Dem-ethylation by CYP3A4 is the primary metabolic pathway for clobazam, with CYP2C19 playing a role as well 35. Metabolism of clobazam results in the formation of N-desmethylclobazam (N-CLB), an active metabolite with antiepileptic potency approximately equivalent to that of diazepam but less than its parent compound 36.…”

“…Metabolism of clobazam results in the formation of N-desmethylclobazam (N-CLB), an active metabolite with antiepileptic potency approximately equivalent to that of diazepam but less than its parent compound 36. This metabolite is formed, slowly reaching T max in approximately 60 hours 35. The half-life ( t 1/2 ) of clobazam appears to be shortened in patients experiencing seizures.…”