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CYP2C19 genetics in fatal carisoprodol intoxications

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Abstract

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.

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Acknowledgements

The authors are grateful to Eleni Aklillu for providing genotype frequencies in control group B and to Asbjørg Christophersen and Ritva Karinen for organising the blood samples. We also thank Linda Uthus and Ida Mari Haugom for genotyping the postmortem samples.

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Authors and Affiliations

  1. Center for Psychopharmacology, Diakonhjemmet Hospital, Forskningsveien 7, PB 85–Vinderen, 0319, Oslo, Norway

    Gudrun Høiseth & Espen Molden

  2. Faculty of Medicine, University of Oslo, Oslo, Norway

    Umair Majid

  3. Norwegian Institute of Public Health, Oslo, Norway

    Jørg Mørland & Jørgen G. Bramness

  4. Department of Clinical Pharmacology, University of Oslo, Oslo, Norway

    Jørg Mørland

  5. Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway

    Jørgen G. Bramness

  6. School of Pharmacy, University of Oslo, Oslo, Norway

    Espen Molden

Authors
  1. Gudrun Høiseth
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  2. Umair Majid
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  3. Jørg Mørland
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  4. Jørgen G. Bramness
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  5. Espen Molden
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Corresponding author

Correspondence to Gudrun Høiseth.

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Høiseth, G., Majid, U., Mørland, J. et al. CYP2C19 genetics in fatal carisoprodol intoxications. Eur J Clin Pharmacol 68, 1561–1565 (2012). https://doi.org/10.1007/s00228-012-1278-6

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  • DOI: https://doi.org/10.1007/s00228-012-1278-6

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