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Postmortem Blood Concentrations of R ‐ and S ‐Enantiomers of Methadone and EDDP in Drug Users: Influence of Co‐Medication and P‐glycoprotein Genotype
Author(s) -
Buchard Anders,
Linnet Kristian,
Johansen Sys Stybe,
Munkholm Julie,
Fregerslev Michael,
Morling Niels
Publication year - 2010
Publication title -
journal of forensic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.715
H-Index - 96
eISSN - 1556-4029
pISSN - 0022-1198
DOI - 10.1111/j.1556-4029.2009.01278.x
Subject(s) - methadone , pharmacology , metabolite , pharmacogenetics , medicine , pharmacokinetics , drug , genotype , methadone maintenance , chemistry , gene , biochemistry
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.