Madadi Parvaz, Ciszkowski Catherine, Gaedigk Andrea, Leeder J Steven, Teitelbaum Ronni, Chitayat David, Koren Gideon
Division of Clinical Pharmacology and Toxicology, and the Motherisk Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
Curr Drug Saf. 2011 Feb 1;6(1):36-9. doi: 10.2174/157488611794479991.
The pro-drug codeine is commonly prescribed for postpartum pain relief in North America. The safety of codeine during breastfeeding is related in part to the extent of the active morphine metabolite catalyzed from codeine via the cytochrome P450 2D6 (CYP2D6) enzyme. In mothers who have greater than two functional copies of the CYP2D6 gene (CYP2D6 ultrarapid metabolism phenotype; UM) a substantially higher proportion of morphine is produced. Label changes on codeine-containing medications will highlight the risks associated with this genotype for breastfeeding mothers, but are not supported by translation strategies on how to incorporate this pharmacogenetic knowledge into clinical practice. To address the immediate issue of CYP2D6 UM inheritance in family members of a breastfed infant who succumbed to fatal opioid intoxication and whose codeine-prescribed mother was a CYP2D6 UM, we constructed a pedigree. While the pedigree approach is helpful to aid diagnosis, identify other at risk family members, and simplify pharmacogenetic analysis, its clinical usefulness is dependant on an institutional framework which is not available in most centers at this time.
在北美，前体药物可待因常用于产后止痛。可待因在母乳喂养期间的安全性部分与通过细胞色素P450 2D6（CYP2D6）酶从可待因催化生成的活性吗啡代谢物的程度有关。在具有两个以上CYP2D6基因功能拷贝的母亲中（CYP2D6超快代谢表型；UM），吗啡的生成比例显著更高。含可待因药物的标签变更将突出这种基因型给母乳喂养母亲带来的风险，但对于如何将这种药物遗传学知识纳入临床实践，却没有相应的转化策略支持。为了解决一名母乳喂养婴儿因致命性阿片类药物中毒死亡且其母亲因开具可待因处方而属于CYP2D6 UM这一事件中，该婴儿家庭成员的CYP2D6 UM遗传这一紧迫问题，我们构建了一个家系图谱。虽然家系图谱方法有助于辅助诊断、识别其他有风险的家庭成员并简化药物遗传学分析，但其临床实用性取决于一个机构框架，而目前大多数中心都没有这样的框架。
