Antemortem conversion of codeine to morphine in man

Area of Science:

• Forensic Toxicology
• Pharmacokinetics
• Drug Metabolism

Background:

• Codeine is a widely used analgesic and antitussive medication.
• Understanding codeine's metabolic pathways is crucial for interpreting toxicological findings in overdose cases.
• Previous studies have suggested codeine can be converted to morphine in the body.

Purpose of the Study:

• To investigate the metabolic relationship between codeine and morphine in postmortem drug overdose cases.
• To determine the extent of codeine to morphine conversion in various biological specimens.
• To assess the stability of codeine and its metabolites in postmortem tissues under controlled conditions.

Main Methods:

• Analysis of codeine and morphine concentrations in blood, bile, liver, kidney, and urine from 45 drug overdose cases.
• Comparison of codeine to morphine ratios across different biological matrices.
• In-vitro studies to evaluate codeine demethylation in postmortem tissues stored at cold temperatures.

Main Results:

• Evidence of codeine metabolism to morphine was observed in antemortem specimens.
• Morphine concentrations were generally lower than codeine in blood, liver, kidney, and urine.
• Bile samples exhibited higher morphine concentrations than codeine, suggesting significant hepatic demethylation.
• Controlled in-vitro studies confirmed no codeine demethylation in postmortem tissues during 30 days of cold storage.

Conclusions:

• Codeine undergoes partial metabolism to morphine in the antemortem stage.
• The liver plays a significant role in the demethylation of codeine to morphine.
• Postmortem tissue analysis is reliable for codeine and morphine levels, as cold storage prevents in-vitro demethylation.