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Forensic Sci Int. 2014 Jun;239:50-6. doi: 10.1016/j.forsciint.2014.03.018. Epub 2014 Mar 26.

Codeine-related deaths: The role of pharmacogenetics and drug interactions.

Author information

1
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Canada.
2
Toxicology Section, Centre of Forensic Sciences, Toronto, Canada.
3
Department of Medical Genetics, Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, Children's and Women's Health Centre of British Columbia, Vancouver, Canada.
4
Child and Family Research Institute, Children's and Women's Health Centre of British Columbia, Vancouver, Canada; Pharmaceutical Outcomes Programme, Children's and Women's Health Center of British Columbia, Vancouver, Canada; Department of Paediatrics, Division of Translational Therapeutics, University of British Columbia, Vancouver, Canada.
5
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Canada; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.
6
Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Canada; Toxicology Section, Centre of Forensic Sciences, Toronto, Canada. Electronic address: parvaz.madadi@gmail.com.

Abstract

The objective of this study was to assess the relationship between genetic polymorphisms and drug interactions on codeine and morphine concentrations in codeine-related deaths (CRD). All CRD in Ontario, Canada between 2006 and 2008 were identified. Post-mortem blood was analyzed for 22 polymorphisms in 5 genes involved in codeine metabolism and response. Sixty-eight CRD were included in this study. The morphine-to-codeine ratio was significantly correlated with the presence of a CYP2D6 inhibitor at varying potencies (p=0.0011). The presence of other central nervous system (CNS) depressants (i.e. benzodiazepines, hypnotics, and/or alcohol) was significantly associated with lower codeine concentration as compared to CRD in which other CNS depressants were not detected (p=0.0002). Individuals who carried the ABCB1 1236T variant had significantly lower morphine concentrations (p=0.004). In this population of individuals whose cause of death was related to codeine, drug interactions and genetic polymorphisms were significantly associated with post-mortem codeine and morphine concentrations.

KEYWORDS:

ABCB1; CYP2D6; Codeine; Drug interactions; Pharmacogenetics; Post-mortem

PMID:
24747667
DOI:
10.1016/j.forsciint.2014.03.018
[Indexed for MEDLINE]

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