非瓣膜性心房颤动患者利伐沙班群体药代动力学研究

陈敏; 陈慧; 林玮玮; 高红瑾; 林伟; 孙红

doi:10.13201/j.issn.1001-1439.2020.08.010

非瓣膜性心房颤动患者利伐沙班群体药代动力学研究

- 1. 福建医科大学省立临床学院福建省立医院药学部(福州, 350001);
- 2. 福建医科大学省立临床学院福建省立医院高血压实验室福建省心血管病研究所;
- 3. 福建医科大学附属第一医院药剂科;
- 4. 福建医科大学省立临床学院福建省立医院保健办
基金项目:
福建省自然科学基金项目(No:2019J01177)

详细信息

通讯作者: 孙红,E-mail:sunhong0707@163.com

中图分类号: R541.7

收稿日期: 2020-05-18

Population pharmacokinetics of rivaroxaban in patients with non-valvular atrial fibrillation

- 1. Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, China;
- 2. Hypertension Laboratory, Provincial Clinical College of Fujian Medical University, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial Hospital;
- 3. Department of Pharmacy, The First Affiliated Hospital Of Fujian Medical University;
- 4. Department of health, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital

More Information

Corresponding author: SUN Hong, E-mail: sunhong0707@163.com

Received Date: 18 May 2020

摘要

摘要: 目的:建立非瓣膜性心房颤动(NVAF)患者利伐沙班群体药代动力学(PPK)模型,为临床个体化给药提供参考。方法:根据入选标准筛选纳入服用利伐沙班的NVAF患者132例,以HPLC-MS/MS法测定利伐沙班血药浓度,用Sanger法测序对ABCB1的3435C>T、1236C>T和2236G>A进行位点分型,用NONMEM法建立NVAF患者利伐沙班PPK模型,并使用Bootstrap和NPDE法验证。结果:PPK最终模型为:CL/F(L/h)=7.6×(GFR/80)^0.429,V/F(L)=106。结论:肾小球滤过率是影响NVAF患者利伐沙班清除率的重要因素。本研究建立的NVAF患者利伐沙班PPK模型稳定、可靠,有较好的预测能力,对临床NVAF患者利伐沙班个体化给药具有实用价值。
- 心房颤动,非瓣膜性 /
- 利伐沙班 /
- 群体药代动力学 /
- 基因多态性 /
- 个体化给药
Abstract: Objective:To establish the population pharmacokinetic(PPK) model of rivaroxaban in patients with non-valvular atrial fibrillation,and provide a reference for clinical development of individualized modes of administration.Method:According to the inclusion and exclusion criteria,132 patients with non-valvular atrial fibrillation were screened and given rivaroxaban.Rivaroxaban plasma concentration was determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The three single nucleotide polymorphisms(ABCB1 3435 C>T,1236 C>T,and 2236 G>A) were detected by Dideoxy chain termination method(Sanger method).The PPK model was developed by Nonlinear Mixed Effects modeling(NONMEM) software.Bootstrap method and the Normalised prediction distribution error(NPDE) method were utilized to evaluate the model.Result:The established PPK model was:CL/F(L/h)=7.6×(GFR/80)^0.429,V/F(L)=106.Conclusion:The glomerular filtration rate is a significant factor on rivaroxaban CL/F in patients with non-valvular atrial fibrillation.Our study's established PPK model is stable,reliable and has good predictive performance,which has practical value for the dosage individualization of rivaroxaban in non-valvular atrial fibrillation patients.
- non-valvular atrial fibrillation /
- rivaroxaban /
- population pharmacokinetics /
- genetic polymorphism /
- dosage individualization

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