Postmortem Redistribution of Fentanyl in the Rabbit Blood

Abstract

Postmortem redistribution of fentanyl in the rabbit was investigated after application of the 50-μg/h Durogesic pain patch. Patches were applied for 48 hours. Two cycles of patch administration were used before characterization of the postmortem redistribution. Fentanyl showed marked redistribution into the femoral and pulmonary veins of the rabbit through 48 hours after the animals were humanely killed and the pain patches removed. The plasma concentration of 2.34 ng/mL in the femoral blood before killing the animals increased 5.6-fold by 48 hours after patch removal to 13.2 ng/mL. This postmortem concentration is approximately 3-fold the C(max) determined during antemortem pharmacokinetic analysis, 4 ng/mL, which was achieved 24 hours after the application of the second 50-μg/h Durogesic pain patch. After blood sampling for 48 hours after animal termination with patch removal compared with sampling for 48 hours from animals not terminated and with patch removal, the exposure ratios in the terminated animals were approximately 30-fold, indicating that between the postmortem redistribution of fentanyl and the cessation of hepatic clearance of fentanyl in the rabbit, the postmortem redistribution of fentanyl leads to an elevated measures of postmortem blood concentrations relative to antemortem blood concentrations.

Postmortem Fentanyl Concentrations: A Review

“…In an attempt to investigate fentanyl PMR, rabbits were assessed after the application 50 µg/h Duragesic ® patches [74]. In a study sponsored by the Johnson & Johnson Pharmaceutical company, two cycles of patch administration were applied and plasma fentanyl concentrations were determined following animal termination with patch removal and compared to animals that were not terminated with patch removal.…”

“…Secondly, rabbits have been demonstrated to have a 3-fold faster metabolism than man [74], which would acutely affect fentanyl blood concentrations during the patch treatment period. These considerable pharmacokinetic differences compared to humans most likely account for the need to apply such a large 50 µg/h dose (to 7.5 pound animals) to achieve what was considered "therapeutic concentrations of fentanyl in the rabbits", and thereby make direct comparison to human subjects imprudent.…”

Time-dependent postmortem redistribution of butyrfentanyl and its metabolites in blood and alternative matrices in a case of butyrfentanyl intoxication

“…lipophilicity or pKa. Giving the structural similarities to fentanyla drug that is known for significant postmortem concentration increases in peripheral blood [21,22] -PMR of butyrfentanyl seems to be likely. The aim of this work was to investigate tissue distribution and time-dependent PMR of butyrfentanyl and its main metabolites.…”

An Examination of the Postmortem Redistribution of Fentanyl and Interlaboratory Variability,

“…This has been previously demonstrated eloquently in an animal model by Ceelen et al. who used rabbits exposed to fentanyl patches to show a linear increase in the femoral blood fentanyl concentration after death, presumably from release from muscle stores. Another group used a similar study design to look at postmortem redistribution .…”