华法林药物基因组学的研究推动其个体化医疗的进程

药物基因组学可以帮助人们更好地认识药物与机体之间的相互作用。华法林是临床上广泛使用的香豆素类口服抗凝血药,其狭窄的抗凝治疗指数范围和抗凝不当所致的并发症一直困扰着临床医师,如何合理使用已经成为一个难题。近年来,随着药物基因组学的快速发展,研究发现药动学和药效学多个相关基因的多态性造成了个体差异,影响了华法林的使用剂量。本文综述了药物基因组学研究在华法林用药中的国内外最新进展,为华法林个体化医疗提供参考依据。

Pharmacogenomic research advances in warfarin individualized therapy

Pharmacogenomic information may allow predictions about effective drug dosage and therapeutic and toxic effects to be made prior to drug administration. Warfarin is the most widely used oral anticoagulant in the world for patients with venous thrombosis, pulmonary embolism, chronic atrial fibrillation, and prosthetic heart valves. Warfarin therapy, however, can be difficult to manage because of the drug′s narrow therapentic index and the wide individual variability in patient response. With rapid development of pharmacogenomics, approximately 30 genes in pharmacokinetics and pharmacodynamics have been found to contribute to therapeutic effects of warfarin, and genetic polymorphisms in these genes may modulate its anticoagulant activity. The review summarizes the latest pharmacogeomic information of warfarin. Effective clinical translation would establish warfarin pharmacogenomics as a heuristic model for its individualized therapy.