Pediatric Heme/Onc, Vanderbilt University/Monroe Carell Jr Children's Hospital, Nashville, Tennessee, USA.
Pediatr Blood Cancer. 2013 Sep;60(9):1402-7. doi: 10.1002/pbc.24592. Epub 2013 May 16.
Warfarin is the most commonly used oral anticoagulant worldwide. Warfarin has a narrow therapeutic index, requiring frequent monitoring of the INR to achieve therapeutic anticoagulation. The role of pharmacogenomics in warfarin disposition and response has been well established in adults, but remains unclear for pediatric patients. In this review, we focus on the important CYP2C9 and VKORC1 variants involved in warfarin response, our current understanding of warfarin disposition and pharmacogenomics, and recent warfarin pharmacogenetic studies in pediatric patients. Finally, we discuss the need for future pediatric studies and the clinical implications of developing pharmacogenetic-based dosing algorithms in children.
华法林是世界范围内最常用的口服抗凝药物。华法林的治疗指数较窄,需要经常监测 INR 以达到治疗性抗凝。药物基因组学在华法林的处置和反应中的作用在成人中已得到充分证实,但在儿科患者中仍不清楚。在这篇综述中,我们重点介绍了与华法林反应相关的重要 CYP2C9 和 VKORC1 变体、我们目前对华法林处置和药物基因组学的理解,以及最近在儿科患者中进行的华法林药物遗传学研究。最后,我们讨论了未来儿科研究的必要性以及在儿童中开发基于药物遗传学的剂量算法的临床意义。