title: Postmortem blood concentrations of R- and S-enantiomers of methadone and EDDP in drug users: influence of co-medication and p-glycoprotein genotype.
abstract: We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S-enantiomers (Wilcoxon's test, p < 0.001). The samples were divided into four groups according to other drugs detected (methadone only, methadone and strong analgesics, methadone and benzodiazepines, or methadone and other drugs). There was no significant difference in any of the R-methadone/total methadone ratios among the four groups. The median R/S ratio was 1.38, which tends to be higher than that reported for the plasma of living subjects. In addition, we investigated whether small nucleotide polymorphisms in the MDR1 gene that encode the drug transporter P-glycoprotein were associated with the concentrations of R- and S-methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. No significant association was detected.
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. anders.buchard@forensic.ku.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Buchard
authors.forename: Kristian
authors.initials: K
authors.lastname: Linnet
authors.forename: Sys Stybe
authors.initials: SS
authors.lastname: Johansen
authors.forename: Julie
authors.initials: J
authors.lastname: Munkholm
authors.forename: Michael
authors.initials: M
authors.lastname: Fregerslev
authors.forename: Niels
authors.initials: N
authors.lastname: Morling
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000700:Analgesics / Q000097:blood; D001569:Benzodiazepines / Q000097:blood; D005260:Female; D053803:Forensic Genetics; D053593:Forensic Toxicology; D005838:Genotype; D006801:Humans; D008297:Male; D008691:Methadone / Q000097:blood* / Q000737:chemistry / Q000506:poisoning; D008875:Middle Aged; D009294:Narcotics / Q000097:blood* / Q000737:chemistry / Q000506:poisoning; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011180:Postmortem Changes; D011759:Pyrrolidines / Q000097:blood* / Q000737:chemistry; D013237:Stereoisomerism; D019966:Substance-Related Disorders / Q000097:blood
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000700:Analgesics; D009294:Narcotics; D011759:Pyrrolidines; D001569:Benzodiazepines; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine