Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype

Authors

  • Anders Buchard M.Sc.,

    1. Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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  • Kristian Linnet M.D., D.M.Sc.,

    1. Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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  • Sys Stybe Johansen Ph.D.,

    1. Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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  • Julie Munkholm M.D.,

    1. Section of Forensic Pathology, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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  • Michael Fregerslev M.D.,

    1. Section of Forensic Pathology, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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  • Niels Morling M.D., D.M.Sc.

    1. Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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Additional information and reprint requests:
Anders Buchard, M.Sc.
Section of Forensic Genetics
Department of Forensic Medicine
Faculty of Health Sciences
University of Copenhagen
Frederik V’s Vej 11
Copenhagen DK-2100
Denmark
E-mail: anders.buchard@forensic.ku.dk

Abstract

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, < 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.

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