Antemortem conversion of codeine to morphine in man

Forty-five drug overdose cases involving codeine were investigated. Concentrations of codeine and morphine were determined in blood, bile, liver, kidney, and urine. Ratios of codeine to morphine values for each of these specimens were compared and evidence was developed that codeine was metabolized partially into morphine in the antemortem stage. Morphine concentration was less than that of codeine in blood, liver, kidney, and urine. However, bile analyses showed that the amount of morphine exceeded that of codeine, suggesting a more active demethylation activity in the hepatic system than in the blood and other tissues studied. Controlled-in-vitro studies showed that no codeine demethylation occurred in postmortem tissues during cold storage for a period as long as 30 days.