Post-mortem redistribution of three beta-blockers in the rabbit

Area of Science:

• Forensic Science
• Pharmacology
• Toxicology

Background:

• Post-mortem redistribution (PMR) of drugs is a critical factor in forensic toxicology.
• Understanding the influence of drug physico-chemical properties on PMR is essential for accurate interpretation of toxicological findings.

Purpose of the Study:

• To investigate the role of drug lipophilicity in post-mortem redistribution.
• To determine how varying lipophilicity influences drug concentrations in different post-mortem biological samples.

Main Methods:

• An experimental rabbit model was used to study three beta-blockers (atenolol, metoprolol, propranolol) with similar pKa and increasing lipophilicity (Kp).
• Drugs were administered intravenously, and animals were euthanized. Post-mortem samples (fluids and tissues) were collected at various time points (0-48 hours).
• Drug concentrations were quantified using validated liquid chromatography-electrospray-mass spectrometry.

Main Results:

• Lipophilicity significantly influenced the post-mortem redistribution of beta-blockers in specific sites, including the stomach, lungs, cardiac muscle, cardiac blood, and liver.
• The influence of lipophilicity on drug distribution was not observed in all anatomical sites, such as the brain and vitreous humor.
• Concentrations varied across different tissues and fluids over the 48-hour post-mortem interval.

Conclusions:

• Drug lipophilicity is a key determinant of post-mortem redistribution, but its effect is site-specific.
• These findings are crucial for improving the interpretation of drug concentrations in post-mortem forensic investigations.
• Further research into other physico-chemical properties and their impact on PMR is warranted.