Clinical consequences related to a defective elimination of clobazam caused by homozygous mutated CYP2C19 allele

Abstract

Introduction: Voluntary drug intoxication with benzodiazepines is common and in most cases without consequences. We report an interesting case of voluntary drug intoxication with clobazam (CLB) in a patient with a homozygous mutated CYP2C19 genotype.

Case report: A 63-year-old Caucasian man was admitted to an intensive care unit for voluntary drug intoxication with CLB (1200 mg) complicated by prolonged hospitalization (46 days). The levels of CLB and N-desmethylclobazam (NCLB) in plasma were initially 8.3 and 14.8 mg/L. The persistence of a high concentration of NCLB (14.3 mg/L on day 30) suggested a lack of elimination. A homozygous mutated allele of CYP2C19*2 without enzyme activity was discovered. To overcome this phenotype, NCLB metabolism was induced by administering 100 mg of phenobarbital for 10 days, allowing patient improvement.

Discussion: NCLB is the major active metabolite of CLB with a longer half-life and much higher steady-state plasma concentrations compared to the parent drug. The half-life elimination of CLB is 18 h that of NCLB is between 40 and 50 h. However, there is considerable inter-individual variation in the metabolism of CLB and of the report NCLB/CLB under the dependence of genotype of CYP2C19. These polymorphisms are not generally well-known by physicians and may lead to severe poisoning.

Keywords:

• Clobazam
• poisoning
• CYP2C19
• polymorphism
• metabolic

Disclosure statement

No potential conflict of interest was reported by the authors.