Post-mortem redistribution of fentanyl in the rabbit blood

Postmortem redistribution of fentanyl in the rabbit was investigated after application of the 50 µg/hour Durogesic® pain patch. Patches were applied for 48 hours. Two cycles of patch administration were used prior to 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 sacrificed and the pain patches removed. The plasma concentration of 2.34 ng/ml in the femoral blood before sacrificing the animals increased 5.6-fold by 48 hours after patch removal to 13.2 ng/ml. This postmortem concentration is about 3-fold the Cmax determined during antemortem pharmacokinetic analysis, 4 ng/ml, which was achieved 24 hours after the application of the second 50 µg/hour Durogesic® pain patch. Following blood sampling for 48 hours after animal termination with patch removal compared to sampling for 48 hours from animals not terminated and with patch removal the exposure ratios in 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 measurement of postmortem blood concentrations relative to antemortem blood concentrations.