基于蒙特卡罗模拟优化不同肾功能分级患者的利伐沙班抗凝方案  

Monte Carlo simulation-based optimization of the rivaroxaban regimen for anticoagulation in patients with different classes of renal function

作　　者：余巧玲 翟葳葳 李宇蒙 靳盼盼 邱博[2,3] 吴惠珍 YU Qiaoling;ZHAI Weiwei;LI Yumeng;JIN Panpan;QIU Bo;WU Huizhen(Graduate School,Hebei Medical University,Shijiazhuang 050017,China;Dept.of Pharmacy,Hebei General Hospital,Shijiazhuang 050051,China;Hebei Key Laboratory of Clinical Pharmacy,Shijiazhuang 050051,China)

机构地区：[1]河北医科大学研究生学院,石家庄050017 [2]河北省人民医院药学部,石家庄050051 [3]河北省临床药学重点实验室,石家庄050051

出　　处：《中国药房》2024年第24期3016-3022,共7页China Pharmacy

基　　金：河北省自然科学基金项目(No.H2020307020)。

摘　　要：目的优化不同肾功能分级患者的利伐沙班抗凝给药方案。方法根据利伐沙班药品说明书及患者实际服药情况设定给药方案,根据河北省人民医院患者利伐沙班谷浓度参考范围及国际血液学标准化委员会推荐的利伐沙班实验室监测浓度参考范围,设置目标浓度范围区间及分段区间,采用OracleCrystalBall软件(V11.1.2.4),通过蒙特卡罗模拟考察不同给药方案的利伐沙班稳态谷浓度落在各目标浓度范围区间的中靶概率。结果共纳入非瓣膜性房颤患者97例,其检测利伐沙班稳态谷浓度125次、中位稳态谷浓度为32.2 ng/mL;共纳入静脉血栓患者121例,其检测利伐沙班稳态谷浓度159次、中位稳态谷浓度为31.0 ng/mL。非瓣膜性房颤患者的稳态谷浓度参考范围为12~137、3~153 ng/mL,静脉血栓患者的稳态谷浓度参考范围为6~239、3~224 ng/mL。蒙特卡罗模拟结果显示,对于非瓣膜性房颤患者,当肾小球滤过率(eGFR)为0~30mL/min时,其利伐沙班最佳给药方案为每次5mg,每天1次;当eGFR为>30~60mL/min时,其利伐沙班最佳给药方案为每次10~20mg,每天1次或每次5mg,每天2次;当eGFR为>60~90 mL/min时,其利伐沙班最佳给药方案为每次15~30 mg,每天1次或每次5~10 mg,每天2次;当eGFR为>90~120 mL/min时,其利伐沙班最佳给药方案为每次25~30 mg,每天1次或每次5~15 mg,每天2次。对于静脉血栓患者,当eGFR为0~30mL/min时,不推荐每天使用利伐沙班超过5mg;当eGFR为>30~60mL/min时,其利伐沙班最佳给药方案为每次5mg,每天1次;当eGFR为>60~90mL/min时,其利伐沙班最佳给药方案为每次25~30mg,每天1次或每次5~15mg,每天2次;当eGFR为>90~120 mL/min时,其利伐沙班最佳给药方案为每次10~15 mg,每天2次。结论临床对肾功能严重损伤的患者应谨慎选择利伐沙班抗凝。利伐沙班谷浓度参考范围宽泛、个体差异性大,可通过蒙特卡罗模拟方法,结合患者肾功能,个体化选择利伐沙班服药剂�OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels.METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient.The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology.The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software(V11.1.2.4).RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL;a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL.The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL,while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL.Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation,the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate(eGFR)0-30 mL/min was 5 mg once daily;for patients with eGFR>30-60 mL/min,the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily;for patients with eGFR>60-90 mL/min,the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily;for patients with eGFR>90-120 mL/min,the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily.For patients with venous thrombosis,it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min;

关 键 词：利伐沙班 肾功能分级 蒙特卡罗模拟 抗凝方案 非瓣膜性房颤 静脉血栓 

分 类 号：R969.3[医药卫生—药理学] R9732[医药卫生—药学]