Ceelen Liesbeth, De Zwart Loeckie, Voets Marieke, Hillewaert Vera, Monbaliu Johan, Teuns Greet, Coussement Werner, Greway Tony
Department of Toxicology, Dermato-Cosmetology and Pharmacognosy, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Am J Forensic Med Pathol. 2012 Jun;33(2):119-23. doi: 10.1097/PAF.0b013e3181fbbb49.
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.
在应用50μg/h的多瑞吉止痛贴后，研究了芬太尼在兔体内的死后再分布情况。止痛贴应用48小时。在对死后再分布进行特征描述之前，使用了两个周期的贴剂给药。在动物被安乐处死并移除止痛贴后的48小时内，芬太尼在兔的股静脉和肺静脉中显示出明显的再分布。处死动物前股血中2.34 ng/mL的血浆浓度在移除贴剂后48小时增加了5.6倍，达到13.2 ng/mL。该死后浓度约为生前药代动力学分析中确定的C(max)（4 ng/mL）的3倍，C(max)是在第二次应用50μg/h的多瑞吉止痛贴24小时后达到的。与未处死且移除贴剂的动物进行48小时采血相比，处死动物并移除贴剂后进行48小时采血，处死动物的暴露比约为30倍，这表明在兔体内芬太尼的死后再分布和芬太尼肝脏清除的停止之间，芬太尼的死后再分布导致死后血药浓度相对于生前血药浓度升高。
