|Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery|
|Jia, Zaishen1; Tian, Ganzhong2; Ren, Yupeng2; Sun, Zhiquan1; Lu, Wei2; Hou, Xiaotong1|
|关键词||Cardiopulmonary bypass Cardiac surgery Pharmacokinetic model Unfractionated heparin|
|刊名||JOURNAL OF TRANSLATIONAL MEDICINE|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, Research & Experimental|
|研究领域[WOS]||Research & Experimental Medicine|
|关键词[WOS]||MOLECULAR-WEIGHT HEPARIN ; HEALTHY-SUBJECTS ; PROTAMINE ; HEMODIALYSIS ; ENOXAPARIN ; REVERSAL|
Background: Unfractionated heparin (UFH) is widely used as a reversible anti-coagulant in cardiopulmonary bypass (CPB). However, the pharmacokinetic characteristics of UFH in CPB surgeries remain unknown because of the lack of means to directly determine plasma UFH concentrations. The aim of this study was to establish a pharmacokinetic model to predict plasma UFH concentrations at the end of CPB for optimal neutralization with protamine sulfate.
Methods: Forty-one patients undergoing CPB during cardiac surgery were enrolled in this observational clinical study of UFH pharmacokinetics. Patients received intravenous injections of UFH, and plasma anti-F-IIa activity was measured with commercial anti-F-IIa assay kits. A population pharmacokinetic model was established by using nonlinear mixed-effects modeling (NONMEM) software and validated by visual predictive check and Bootstrap analyses. Estimated parameters in the final model were used to simulate additional protamine administration after cardiac surgery in order to eliminate heparin rebound. Plans for postoperative protamine intravenous injections and infusions were quantitatively compared and evaluated during the simulation.
Results: A two-compartment pharmacokinetic model with first-order elimination provided the best fit. Subsequent simulation of postoperative protamine administration suggested that a lower-dose protamine infusion over 24 h may provide better elimination and prevent heparin rebound than bolus injection and other infusion regimens that have higher infusion rates and shorter duration.
Conclusion: A two-compartment model accurately reflects the pharmacokinetics of UFH in Chinese patients during CPB and can be used to explain postoperative heparin rebound after protamine neutralization. Simulations suggest a 24-h protamine infusion is more effective for heparin rebound prevention than a 6-h protamine infusion.
|项目编号||81270327 ; 81470528|
|资助机构||Research Fund of Capital Medical Development ; National Natural Science Foundation of China|
|作者单位||1.Capital Med Univ, Dept Extracorporeal Circulat, Ctr Cardiac Intens Care, Beijing Anzhen Hosp,Beijing Inst Heart Lung & Blo, Beijing 100029, Peoples R China|
2.Peking Univ, Hlth Sci Ctr, Dept Pharmaceut, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
|Jia, Zaishen,Tian, Ganzhong,Ren, Yupeng,et al. Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2015,13.|
|APA||Jia, Zaishen,Tian, Ganzhong,Ren, Yupeng,Sun, Zhiquan,Lu, Wei,&Hou, Xiaotong.(2015).Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery.JOURNAL OF TRANSLATIONAL MEDICINE,13.|
|MLA||Jia, Zaishen,et al."Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery".JOURNAL OF TRANSLATIONAL MEDICINE 13(2015).|