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1. Eur J Clin Pharmacol. 2012 Apr 15. [Epub ahead of print]

CYP2C19 genetics in fatal carisoprodol intoxications.

Høiseth G, Majid U, Mørland J, Bramness JG, Molden E.

Center for Psychopharmacology, Diakonhjemmet Hospital, Forskningsveien 7, PB
85-Vinderen, 0319, Oslo, Norway, gudrun.hoiseth@fhi.no.

INTRODUCTION: Carisoprodol, a frequently used muscle relaxant, can cause
potentially fatal intoxications. Conversion to its active metabolite meprobamate
is almost solely mediated by cytochrome P450 2C19 (CYP2C19), and mutations in
this enzyme could have significant effects on serum concentrations. The objective
of this study was to investigate the role of CYP2C19 genetics in mortalities due
to carisoprodol intoxication. METHODS: The frequencies of CYP2C19 variant alleles
were compared between the study group (n = 75) and two control groups, i.e. (1)
deaths where carisoprodol was detected in the blood of the deceased, but
intoxication was not the cause of death (control group A, n = 38), and (2) a
healthy population not using carisoprodol (control group B, n = 185). In the
study group and control A, the concentrations of carisoprodol and meprobamate
were compared between the different genotype subgroups. RESULTS: The variant
allele frequencies of CYP2C19 did not differ significantly between the study
group and control groups. Moreover, no statistically significant difference in
the concentrations of carisoprodol and meprobamate between the different genotype
subgroups was found. CONCLUSIONS: This study finds no evidence for an important
association between CYP2C19 genetics and mortality risk of carisoprodol. Other
factors, such as co-administration with other drugs, likely play a more important
role.

PMID: 22527345 [PubMed - as supplied by publisher]