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

• NCJ Number: 230728
• Journal: Journal of Forensic Sciences Volume: 55 Issue: 2 Dated: March 2010 Pages: 457-463
• Author(s): Anders Buchard, M.Sc.; Kristian Linnet, M.D., D.M.Sc.; Sys Stybe Johansen, Ph.D.; Julie Munkholm, M.D.; Michael Fregerslev, M.D.; Niels Morling, M.D., D.M.Sc.
• Date Published: March 2010
• Length: 7 pages
• Publication Format: Article
• Publication Type: Report (Study/Research)
• Language: English
• Country: United States of America

Annotation

This study investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples.

Abstract

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 less than 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, the study 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. Tables, figures, and references (Published Abstract)