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

被引：28
|
作者：
Lama, Jessica [1 ,2 ]
Woodall, Karen L. [3 ]
Solbeck, Patricia [3 ]
Ross, Colin J. D. [4 ,5 ]
Carleton, Bruce C. [5 ,6 ,7 ]
Hayden, Michael R. [4 ,5 ]
Koren, Gideon [1 ,2 ,8 ]
Madadi, Parvaz [2 ,3 ]
机构：
[1] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada
[2] Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON M5G 1X8, Canada
[3] Ctr Forens Sci, Toxicol Sect, Toronto, ON M3M 1J8, Canada
[4] Univ British Columbia, Ctr Mol Med & Therapeut, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada
[5] Childrens & Womens Hlth Ctr British Columbia, Child & Family Res Inst, Vancouver, BC, Canada
[6] Childrens & Womens Hlth Ctr British Columbia, Pharmaceut Outcomes Programme, Vancouver, BC, Canada
[7] Univ British Columbia, Div Translat Therapeut, Dept Paediat, Vancouver, BC V5Z 1M9, Canada
[8] Univ Western Ontario, Schulich Sch Med & Dent, Dept Physiol & Pharmacol, London, ON, Canada
来源：
FORENSIC SCIENCE INTERNATIONAL | 2014年 / 239卷
关键词：
Codeine; Pharmacogenetics; Drug interactions; CYP2D6; ABCB1; Post-mortem; METHYLTRANSFERASE COMT GENE; VAL158MET POLYMORPHISM; MORPHINE REQUIREMENTS; NONLINEAR KINETICS; CYP2D6; ACTIVITY; CANCER PAIN; HEROIN; TOXICITY; IMPACT; REDISTRIBUTION;
D O I：
10.1016/j.forsciint.2014.03.018
中图分类号：
DF [法律]; D9 [法律]; R [医药、卫生];
学科分类号：
0301 ; 10 ;
摘要：
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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：50 / 56
页数：7
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