Fentanyl Postmortem Redistribution: Preliminary Findings Regarding the Relationship Among Femoral Blood and Liver and Heart Tissue Concentrations

Luckenbill, Kristin; Thompson, Jonathan; Middleton, Owen; Kloss, Julie; Apple, Fred S.

doi:10.1093/jat/32.8.639

Cited by 34 publications

(18 citation statements)

References 11 publications

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“…The estimated postmortem interval for the presented cases was only four to twelve hours, so any influence from the postmortem interval was likely minimal. Several published reports have indicated postmortem fentanyl blood concentrations, whether specimens are obtained from the heart or femoral artery, are unreliable for the determination of the fentanyl blood concentration at the time of death and ascribing fentanyl overdose as a cause of death (39, 40). However, these assertions have been refuted by considering other physiological and pharmaceutical factors.…”

Section: Discussionmentioning

confidence: 99%

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida

Pearson

Poklis

et al. 2015

Academic Forensic Pathology

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In the last two years, an epidemic of 40 fatal heroin overdose cases has occurred in the Tampa area of Florida. Of these cases, 14 involved fentanyl and acetyl fentanyl. Victim demographics, case histories, toxicology findings, and causes and manners of death for all 40 deaths are presented. In 26 deaths in which acetyl fentanyl or fentanyl were not involved, free and total peripheral blood morphine concentrations were consistent with fatal heroin intoxications, averaging 0.16 mg/L and 0.35 mg/L, respectively. In the heroin cases with fentanyl present (n=7), the average free morphine concentration was 0.040 mg/L, the average total morphine concentration was 0.080 mg/L, and the average fentanyl concentration was 0.012 mg/L. In the cases with heroin, fentanyl, and acetyl fentanyl (n=3), the average free morphine concentration was 0.010 mg/L, the average total morphine concentration was 0.030 mg/L, the average fentanyl concentration was 0.018 mg/L, and the average acetyl fentanyl concentration was 0.008 mg/L. In the cases involving only acetyl fentanyl (without heroin or fentanyl, n=4), the average acetyl fentanyl concentration was 0.47 mg/L and the average acetyl norfentanyl concentration was 0.053 mg/L. The presented cases, with associated drug concentrations, case histories, demographics, and causes and manners of death may help provide assistance with the interpretation of the postmortem findings. Based on case circumstances, autopsy results, and toxicology results, it is evident that fentanyl and/or acetyl fentanyl, when present, contributed to the cause of death.

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Section: Discussionmentioning

confidence: 99%

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida

Pearson

Poklis

et al. 2015

Academic Forensic Pathology

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“…For this reason, the left ventricle tissue was sampled from nine fatalities whose deaths were fentanyl-related. The mean heart to femoral blood ratio was 3.6 (range 1.9-5.4) [118]. Also, high fentanyl concentrations in ventricular tissue were determined by Olson et al [46].…”

Section: Opioidsmentioning

confidence: 88%

“…6.21 with a range of 1.91-12.11 [46]. The above-mentioned ratios were poorly correlated with the postmortem interval [118].…”

Section: Opioidsmentioning

confidence: 91%

“…Since differences among heart and femoral blood are often observed for fentanyl in postmortem examinations, inter alia, it is the myocardium that is suspected of falsely elevating the heart blood fentanyl level [46,118]. In light of that, Luckenbill et al [118] settled the question of the ratio of fentanyl concentration in heart tissue to that in the femoral vein. For this reason, the left ventricle tissue was sampled from nine fatalities whose deaths were fentanyl-related.…”

Section: Opioidsmentioning

confidence: 99%

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Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Tylutki

Polak

2015

Biopharm & Drug Disp

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ABSTRACT:Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart.

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“…For each condition, two independent extractions of urine obtained from drug free volunteers were performed and injected into LC-MS/MS. [34,35,41,80]. A simple protocol (conditioning as described in Section 2.6.1, sample application, washes with H 2 O, acid and MeOH and elution with isopropanol-dichloromethane-ammonium hydroxide (20:78:2)) was used on the silica-based mixed-mode Bond Elut Certify SPE cartridges.…”

Section: Optimal Spe Methods and Lc Methodsmentioning

confidence: 99%

Development and validation of a sensitive ultra performance liquid chromatography tandem mass spectrometry method for the analysis of fentanyl and its major metabolite norfentanyl in urine and whole blood in forensic context

Verplaetse

Tytgat

2010

Journal of Chromatography B

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Fentanyl Postmortem Redistribution: Preliminary Findings Regarding the Relationship Among Femoral Blood and Liver and Heart Tissue Concentrations

Cited by 34 publications

References 11 publications

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Development and validation of a sensitive ultra performance liquid chromatography tandem mass spectrometry method for the analysis of fentanyl and its major metabolite norfentanyl in urine and whole blood in forensic context

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