|Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers|
|Zhang, Dong-mei2; Wang, Kun1; Zhao, Xia2; Li, Yun-fei1; Zheng, Qing-shan1; Wang, Zi-ning2; Cui, Yi-min2|
|关键词||Anticoagulation Therapy Bivalirudin Activated Clotting Time Healthy Young Chinese Subjects Population Pharmacokinetics And Pharmacodynamics|
|刊名||ACTA PHARMACOLOGICA SINICA|
|WOS标题词||Science & Technology|
|类目[WOS]||Chemistry, Multidisciplinary ; Pharmacology & Pharmacy|
|研究领域[WOS]||Chemistry ; Pharmacology & Pharmacy|
|关键词[WOS]||PERCUTANEOUS CORONARY INTERVENTION ; CARDIOPULMONARY BYPASS ; PHARMACOLOGY ; HEPARIN|
Aim: To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects.
Methods: Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activated clotting time (ACT). Population PK-PD analysis was performed using the nonlinear mixed-effects model software NONMEM. The final models were validated with bootstrap and prediction-corrected visual predictive check (pcVPC) approaches.
Results: The final PK model was a two-compartment model without covariates. The typical PK population values of clearance (CL), apparent distribution volume of the central-compartment (V-1), inter-compartmental clearance (Q) and apparent distribution volume of the peripheral compartment (V-2) were 0.323 L.h(-1).kg(-1), 0.086 L/kg, 0.0957 L.h(-1).kg(-1), and 0.0554 L/kg, respectively. The inter-individual variabilities of these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The final PK-PD model was a sigmoid E-max model without the Hill coefficient. In this model, a covariate, red blood cell count (RBC star), had a significant effect on the EC50 value. The typical PD population values of maximum effect (E-max), EC50, baseline ACT value (E-0) and the coefficient of RBC star on EC50 were 318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual variabilities of E-max, EC50, and E-0 were 6.80%, 46.4%, and 4.10%, respectively.
Conclusion: Population PK-PD models of bivalirudin in healthy young Chinese subjects have been developed, which may provide a reference for future use of bivalirudin in China.
|资助机构||Shenzhen Main Luck pharmaceuticals, Inc.|
|作者单位||1.Peking Univ, Hosp 1, Dept Pharm, Beijing 100034, Peoples R China|
2.Shanghai Univ Tradit Chinese Med, Ctr Drug Clin Res, Lab Pharmacometr, Shanghai 201203, Peoples R China
|Zhang, Dong-mei,Wang, Kun,Zhao, Xia,et al. Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers[J]. ACTA PHARMACOLOGICA SINICA,2012,33(11):1387-1394.|
|APA||Zhang, Dong-mei.,Wang, Kun.,Zhao, Xia.,Li, Yun-fei.,Zheng, Qing-shan.,...&Cui, Yi-min.(2012).Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers.ACTA PHARMACOLOGICA SINICA,33(11),1387-1394.|
|MLA||Zhang, Dong-mei,et al."Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers".ACTA PHARMACOLOGICA SINICA 33.11(2012):1387-1394.|