基于群体药动学和药效学模型优化成年感染患者的哌拉西林/他唑巴坦给药方案

Optimizing dosage regimens of piperacillin/tazobactam in adult patients with sepsis based on population pharmacokinetic and pharmacodynamic model

目的:通过哌拉西林群体药动学和药效学特征进行最佳临床给药方案的筛选,确定符合临床疗效靶标的最佳给药方案。方法:应用NONMEM软件对所确定的哌拉西林/他唑巴坦群体药动学模型进行模型仿真,计算不同给药方案下的药动学和药效学数据结果,并根据结果确定最佳给药方案。结果:当MIC=8 mg/L时,只有4 g q8h持续输注可以达到药效100%,而输注3 h和4 h只能达到87.5%。当MIC<=32 mg/L时,4g q8h持续输注均可以达到药效100%,而输注时间3 h和4 h只能达到43.7%和50%。3 g q6h输注30 min与输注3 h疗效相当,持续输注的疗效仍然远远高于输注3 h的给药方式。

AIM： To identify the optimal dosage regimens of piperacillin / tazobactam according to population pharmacokinetic and pharmacodynamics characteristics in order to attain target clinic effect.METHODS： To simulate the vivo data of piperacillin / tazobactam based on population pharmacokinetic and pharmacodynamics model using NONMEM. The pharmacokinetic and pharmacodynamics data were calculated for different dosage regimens and therefore the optimal dosage regimens were acknowledged.RESULTS： The PTA can attain 100% using 4g q8h infusion 8h when MIC equal to 8mg / L,but it was 87. 5% for 3h and 4h infusion. When MIC is greater to 32mg / L,the PTA can attain 100% using4 g q8 h infusion 8h,but it were only 43. 7% and50% for 3h and 4h infusion,respectively. The PTA is identical for 3g q6h infusion 30 min and 3h.CONCLUSION： When MIC〈 = 4 mg / L,the recommended optimal dosage regimen is 4g q8h infusion 3h. When MIC = 〉8mg / L,the recommended optimal dosage regimen is 4g q8h infusion 8h. This study provide a simple,directed and rapid way to check clinical effect of piperacillin / tazobactam and therefore can be used to optimize the dosage regimen.