The role of dihydrocodeine (DHC) metabolites in dihydrocodeine-related deaths

The focus of this study was to report the blood and urine concentrations of dihydrocodeine (DHC) and its metabolites, dihydrocodeine-6-glucuronide (DHC6G), dihydromorphine (DHM), dihydromorphine-3-glucuronide (DHM3G), and dihydromorphine-6-glucuronide (DHM6G) in deaths involving DHC, and to report the range of concentrations detected in real cases in order to understand their contribution to DHC intoxication. Twenty-six positive postmortem cases were involved in the current study. Five cases were attributed solely to DHC intoxication, 13 cases to polydrug intoxication, and the remainder of the cases were unrelated to DHC (DHC has been detected but is unrelated to the cause of death). DHC and its glucuronide were detected in all cases investigated in blood and urine matrices. Unchanged parent drug is the most abundant analyte detected in blood samples mean and median of DHC/total DHC (DHC plus DHC6G) percentages were 63% and 72%, and DHC6G is the most abundant DHC metabolite in urine with a mean and median DHC6G/TDHC of 69% and 70%, respectively. Blood DHC concentrations ranged from 40 to 166,000 ng/mL and 200 to 159,000 ng/mL in urine. DHC6G concentrations in these cases ranged from 20 to 62,180 ng/mL in blood and 40 to 500,000 ng/mL in urine. However, DHM and its glucuronide were present at lower concentrations than DHC and its glucuronide. In the current study, it can be concluded that concentrations of DHC that cause death may be lower in polydrug intoxication. Concentrations found at autopsy overlapped between toxic and therapeutic concentrations because of the presence of other harmful substances, and death can occur with concentrations below lethal concentrations as reported in Case 1 (500 ng/mL). It has been suggested that DHM and DHM6G may play a major role in assessing the cause of death in cases where DHC is not detected and when it is detected in low concentrations. The current study does not support this hypothesis, and it can be seen clearly from the data reported here that DHM and its glucuronide were not detected where DHC was not detected. Toxic concentrations of DHM and DHM6G were identified in some of these cases; however, the concentration of DHC was enough to cause death on its own. It seems that DHM and DHM6G have less influence in causing death than the parent drug itself.