Two drugs detected in the same body need not share the same postmortem distribution. Pounder and Jones documented differing blood-site and tissue patterns in four detailed overdose cases. Their observations support interpreting each analyte separately rather than using one co-detected drug as a correction for another.
A case series with anatomically controlled sampling
The 1990 study selected suspected overdose cases before medicolegal autopsy. Investigators collected multiple tissues and fluids and took blood by needle puncture after ligating or cross-clamping the relevant vessels. This approach helped preserve the distinction between sampling sites.
The four cases involved different drug combinations and different intervals. Autopsy occurred 17 hours after discovery in case 1, an estimated 36 hours after death in case 2, approximately 24–48 hours after death in case 3, and 7.25 hours after death in case 4. These were descriptive individual investigations, not a randomized experiment or a prevalence survey. The methods do not provide a uniform specimen storage or preservative protocol.
Clomipramine and flurazepam peaked at different blood sites
Case 3 concerned a 24-year-old woman reported to have taken chloral hydrate, clomipramine and flurazepam. Across blood sites, clomipramine ranged from 4.0 to 21.5 mg/L and its metabolite desmethylclomipramine from 1.7 to 8.1 mg/L. The highest concentrations were in pulmonary arterial and venous blood, and the lowest in femoral veins.
Flurazepam ranged from 0.15 to 0.99 mg/L. Its highest reported blood concentration was in the infrarenal inferior vena cava, with the lowest in subclavian and femoral veins. Mixed cardiac blood contained clomipramine 15.3 mg/L, desmethylclomipramine 4.1 mg/L and flurazepam 0.51 mg/L. “Cardiac blood” therefore did not represent the maximum for every compound.
Tissue concentrations also differed by drug
In that same case, liver contained clomipramine 298 mg/kg and desmethylclomipramine 58 mg/kg; lung contained 107 and 54 mg/kg, respectively. Flurazepam concentrations were 1.1 mg/kg in liver and 0.42 mg/kg in lung, with 1.5 mg/kg in renal cortex and 4.9 mg/kg in perirenal fat.
These findings describe different tissue distributions. Tissue values in mg/kg should not be treated as numerically interchangeable with blood values in mg/L or used to infer equivalent pharmacological effects across drugs. The measured amount of unabsorbed drug in gastrointestinal contents likewise is a different quantity from a tissue concentration.
A second case provided an informative contrast
Case 4 involved imipramine overdose followed by hospital treatment that included intravenous lidocaine. Imipramine concentrations across postmortem blood sites ranged from 4.1 to 18.1 mg/L, whereas lidocaine ranged from 0.9 to 1.4 mg/L. Liver and lung imipramine were 136 and 100 mg/kg, compared with lidocaine at 1.0 and 0.9 mg/kg.
The contrast illustrates different distributions within one body, but it does not isolate an intrinsic drug effect: dose, route, treatment timing and time available for distribution differed. It cannot establish that lidocaine never redistributes or that every imipramine case follows this pattern.
Mechanistic evidence and analytical limits
The authors proposed diffusion from drug-rich organs, particularly liver and lung, as a major explanation for site differences. They also considered incomplete distribution during life, variable blood composition and postmortem changes. Their case data supported a mechanism; they did not directly measure drug movement over time or prove a single cause.
Tricyclic compounds were quantified by gas chromatography with nitrogen–phosphorus detection, barbiturates by HPLC–UV, and flurazepam-related compounds by gas chromatography with electron-capture detection. Assays used internal standards, five-point calibration, duplicate case analyses and independently prepared controls. Full numerical detection limits, precision and recovery validation were not reported. These were targeted quantitative procedures, not one comprehensive screening method.
Interpret each analyte on its own evidence
The series supplies no universal redistribution factor and no statistical estimate of how often these patterns occur. A drug’s detection, a tissue reservoir and a high autopsy blood concentration are separate findings; none alone establishes the dose, impairment or cause of death.
Review the exact vessel, analyte, method and timing for each result. Our discussion of subclavian versus femoral sampling addresses the additional problem of treating different peripheral sites as equivalent.
Primary source
Pounder DJ, Jones GR. Post-mortem drug redistribution—A toxicological nightmare. Forensic Science International. 1990;45:253–263. doi:10.1016/0379-0738(90)90182-X.
Leave a Reply