药物基因学及临床应用.ppt

* * * * * * * * * * * * * * * * VKORC1 -1639 GA CYP2C9 Starting Dose (mg/d) Frequency n (%) Dose Match n (%) GG *1/*1 5 3 (2.8%) 2(66.7%) GG *1/*3 3.75 0 0 GG *3/*3 3.75 0 0 AG *1/*1 3.75 17 (15.7%) 12(70.5%) AG *1/*3 2.5 1 (0.9%) 1(100%) AG *3/*3 2.5 0 0 AA *1/*1 2.5 83 (76.9%) 58(69.9%) AA *1/*3 1.25 4 (3.7%) 2(50%) AA *3/*3 1.25 0 0 Total n(%) 108(100%) 74(68.5%) 第12周随访华法令的用量分析 第12周随访华法令的用量分析 结果 83％的病患在华法令治疗2周内就可达到血中稳定的治疗INR值。在治疗第4周可达到90%。 治疗第12周，华法令的平均剂量2.76?0.88 mg (1~6 mg)。 。74/108 (69%)预测值与实际值吻合 基因检测对于低(1 mg)或高剂量(5 mg)组特别有帮助 基因检测对低或高剂量华法令组有帮助 NEJM 2009;360:753-64 回归分析 Dose = - 0.432 + 0.769 x predict dose - 0.015 x Age + 1.125 x BSA Dose algorithm: These factors in this model accounted for 48%. R2 = 0.482 Warfarin Sensitivity Test CYP2C9: Polymorphisms produce defective CYP2C9 protein that reduce metabolism of warfarin, thus more sensitive to warfarin VKORC1 (vitamin?K epoxide reductase complex subunit?1): warfarin inhibits VKORC1, and haplotypes associated with change in activity and warfarin dose Verigene? (Nanosphere Inc.) FDA Clears Genetic Lab Test for Warfarin Sensitivity The U.S. Food and Drug Administration today cleared for marketing a new genetic test that will help physicians assess whether a patient may be especially sensitive to the blood-thinning drug warfarin (Coumadin), which is used to prevent potentially fatal clots in blood vessels. One-third of patients receiving warfarin metabolize it quite differently than expected and experience a higher risk of bleeding. Research has shown that some of the unexpected response to warfarin depends on variants of two genes, CYP2C9 and VKORC1. The Nanosphere Verigene Warfarin Metabolism Nucleic Acid Test detects some variants of both genes. Today’s action offers physicians the first FDA cleared genetic test for warfarin sensitivity, which is another step in our commitment to personalized medicine,” said Daniel Schultz, M.D., director, FDA’s Center for Devices and Radiological Health.