title: CYP2C19 genetics in fatal carisoprodol intoxications.
abstract: BACKGROUND
  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.
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Forskningsveien 7, PB 85-Vinderen, 0319, Oslo, Norway. gudrun.hoiseth@fhi.no
authors.forename: Gudrun
authors.initials: G
authors.lastname: Høiseth
authors.forename: Umair
authors.initials: U
authors.lastname: Majid
authors.forename: Jørg
authors.initials: J
authors.lastname: Mørland
authors.forename: Jørgen G
authors.initials: JG
authors.lastname: Bramness
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001344:Autopsy; D001711:Biotransformation; D002328:Carisoprodol / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D002423:Cause of Death; D065731:Cytochrome P-450 CYP2C19; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D008620:Meprobamate / Q000097:blood; D009125:Muscle Relaxants, Central / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D009664:Norway / Q000453:epidemiology; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D009125:Muscle Relaxants, Central; D002328:Carisoprodol; D008620:Meprobamate; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19