title: Codeine-related deaths: The role of pharmacogenetics and drug interactions.
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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lam
authors.affiliation: Toxicology Section, Centre of Forensic Sciences, Toronto, Canada.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Woodall
authors.affiliation: Toxicology Section, Centre of Forensic Sciences, Toronto, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Solbeck
authors.affiliation: 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.
authors.forename: Colin J D
authors.initials: CJ
authors.lastname: Ross
authors.affiliation: 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.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
authors.affiliation: 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.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.affiliation: 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.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.affiliation: 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.
authors.forename: Parvaz
authors.initials: P
authors.lastname: Madadi
mesh_terms: D000328:Adult; D002492:Central Nervous System Depressants; D002853:Chromatography, Liquid; D003061:Codeine / Q000493:pharmacokinetics* / Q000506:poisoning; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000097:blood*; D004347:Drug Interactions; D005260:Female; D053803:Forensic Genetics; D053593:Forensic Toxicology; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000493:pharmacokinetics; D009294:Narcotics / Q000493:pharmacokinetics* / Q000506:poisoning; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D053719:Tandem Mass Spectrometry
chemical_list: D002492:Central Nervous System Depressants; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D009294:Narcotics; D009020:Morphine; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine
keywords: ABCB1; CYP2D6; Codeine; Drug interactions; Pharmacogenetics; Post-mortem