TY - JOUR
T1 - Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype
AU - Buchard, Anders
AU - Linnet, Kristian
AU - Johansen, Sys Stybe
AU - Munkholm, Julie
AU - Fregerslev, Michael
AU - Morling, Niels
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
U2 - 10.1111/j.1556-4029.2009.01278.x
DO - 10.1111/j.1556-4029.2009.01278.x
M3 - Journal article
C2 - 20102450
SN - 0022-1198
VL - 55
SP - 457
EP - 463
JO - Journal of Forensic Sciences
JF - Journal of Forensic Sciences
IS - 2
ER -