An investigation of morphine‐to‐codeine metabolic ratios in postmortem blood, drug interactions, and cytochrome P450 2D6 (CYP2D6) genotype

Abstract

The objective of this study was to investigate the correlation between CYP2D6 genotype, drug interactions, and morphine‐to‐codeine metabolic ratio (MR) in codeine‐related deaths (CRD). The records of the Office of the Chief Coroner of Ontario were examined to identify all CRD from 2006–2008. Deaths in which codeine and its metabolite, morphine, were quantified on the toxicological screen were included. From these, cases in which the manner of death was undetermined, heroin use was suspected, and/or morphine use was suspected were excluded. A total of 59 CRD were included. Postmortem blood samples were analyzed for 17 polymorphisms in CYP2D6 as well as gene duplication. The frequencies of CYP2D6 ultrarapid, extensive, intermediate, and poor metabolizer (PM) was not different in CRDs and a previously published healthy cohort taking opioids. Alcohol use prior to death was significantly associated with CRD that were deemed to be accidental by the coroner (p=0.05). The presence of a selective‐serotonin reuptake inhibitor was significantly associated with suicides (p=0.014). PM was associated with low MR. These findings suggest that CYP2D6 genotype and drug interactions should considered as part of the postmortem toxicological interpretation for CRD, especially in cases with low or high MR.