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Postmortem disposition of morphine in rats
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46223.
Abstract:
The antemortem and postmortem distribution of morphine was studied in rats for the purpose of establishing whether drug distribution is altered after death. Samples were examined for free and total morphine concentration, pH and water content at 0-96 h after death. Morphine was administered antemortem at various intervals. All groups of rats studied showed a significant (P less than 0.05) increase in postmortem cardiac blood morphine concentrations. These changes, which are detectable within 5 min after death are likely to be related to an observed, rapid decrease in cardiac blood pH from 7.34 +/- 0.02 to 6.74 +/- 0.05. Significant increases in free morphine levels were, also, observed 24 and 96 h after death in liver, heart and forebrain while urine morphine levels decreased. The liver showed the greatest increase (20-fold) in free morphine levels 96 h after death, while hindbrain levels did not significantly change. Bacterial hydrolysis of morphine glucuronides accounted only in part for the observed increase in free morphine concentration. Postmortem fluid movement and pH-dependent drug partitioning was detected. It would appear that several mechanisms are responsible for postmortem drug distribution. Understanding the mechanisms and patterns responsible may eventually lead to better choices of postmortem tissue which may better represent antemortem drug levels.
Insights
Postmortem changes significantly alter morphine distribution in rats, with increased concentrations in cardiac blood and tissues like the liver shortly after death. These shifts are linked to pH changes and fluid movement, impacting drug analysis.
Area of Science:
- Forensic Toxicology
- Pharmacokinetics
- Postmortem Studies
Background:
- Understanding postmortem drug distribution is crucial for accurate toxicological analysis.
- Drug concentrations can change significantly after death due to various physiological and chemical processes.
Purpose of the Study:
- To investigate the antemortem and postmortem distribution of morphine in rats.
- To determine if drug distribution patterns are altered after an organism's death.
Main Methods:
- Morphine was administered to rats at various intervals before death.
- Samples of cardiac blood, liver, heart, forebrain, hindbrain, and urine were collected 0-96 hours postmortem.
- Concentrations of free and total morphine, pH, and water content were measured.
Main Results:
- A significant increase in postmortem cardiac blood morphine concentrations was observed within 5 minutes of death, correlating with a rapid decrease in blood pH.
- Free morphine levels increased significantly in the liver, heart, and forebrain 24-96 hours postmortem, while urine levels decreased.
- The liver exhibited a 20-fold increase in free morphine levels by 96 hours postmortem; hindbrain levels remained unchanged.
- Bacterial hydrolysis partially explained increased free morphine, but postmortem fluid shifts and pH-dependent partitioning were also key factors.
Conclusions:
- Postmortem drug distribution is influenced by multiple mechanisms, including pH changes and fluid shifts.
- These findings highlight the dynamic nature of drug concentrations after death.
- Identifying these postmortem distribution patterns may aid in selecting appropriate tissues for toxicological analysis to better reflect antemortem drug levels.
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