CYP2C19 genetics in fatal carisoprodol intoxications.

Abstract

Introduction: Carisoprodol, a frequently used muscle relaxant, can cause potentially fatal intoxications. The drug was primarily used against acute back pain and was been available for nearly 50 years. It was a frequently used drug until its withdrawal from the Norwegian market in 2008 due to studies suggesting that it potentially caused lethal intoxications. Conversion of carisoprodol 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 0 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 0 38), and (2) a healthy population not using carisoprodol (control group B, n 0 185). 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. Keywords: Carisoprodol. Meprobamate. CYP2C19 variant alleles. Intoxication.