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蒙特卡罗模拟评估肾功能不全老年患者使用美罗培南的给药方案
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| 篇名： | 蒙特卡罗模拟评估肾功能不全老年患者使用美罗培南的给药方案 |
| TITLE： | Evaluation of the dosing regimen of meropenem in elderly patients with renal insufficiency with Monte Carlo simulation |
| 摘要： | 目的 探讨美罗培南在肾功能不全的老年患者中合适的给药方案。方法采用美罗培南在老年患者中的二房室群体药动学参数进行蒙特卡罗模拟，模型纳入肾功能对参数的影响，设计给药剂量为0.5、1、2g，给药方式为静脉注射（持续6min）和静脉滴注（0.5、3h），给药频率为q12h、q8h，共计18种给药方案组合，分别计算%fT＞4MIC≥40%和Cmin≤27.5mg/L的达标概率，以优选给药方案。结果对于肌酐清除率（CLcr）≤40mL/min的老年患者，最低抑菌浓度（MIC）为1mg/L时，推荐的给药方案是“0.5g，静脉滴注0.5h，q12h”“1g，静脉注射，q12h”；MIC为2mg/L时，推荐的给药方案是“0.5g，静脉注射，q8h”“1g，静脉滴注0.5h，q12h”；MIC为4、8mg/L时，推荐的给药方案是“1g（或2g），静脉注射，q8h”。对于CLcr为50mL/min的老年患者，MIC为1mg/L时，推荐的给药方案是“0.5g，静脉注射，q8h“”1g，静脉注射，q12h”；MIC为2、4、8mg/L时，推荐的给药方案是“0.5g（或1g，或2g），静脉滴注0.5h，q8h”。上述所有方案的达标概率都在96.6%及以上“。2g，静脉注射或静脉滴注0.5h，q8h”的给药方案在1000次模拟中，约有40次模拟出现Cmin＞27.5mg/L的情况，可能出现神经系统不良反应。结论对于肾功能不全老年患者，美罗培南给药方案应以CLcr＝40mL/min为界进行相应调整，同时警惕神经系统毒性。 |
| ABSTRACT： | OBJECTIVE To explore the appropriate dosing regimen of meropenem in the elderly with renal insufficiency. METHODS The meropenem population pharmacokinetics of the two-compartment model of elderly patients were applied for Monte Carlo simulation. The model included the effect of renal function on the parameters. The designed dosages were 0.5， 1， 2 g； the administration modes included intravenous injection （lasting for 6 min） and intravenous drip （0.5， 3 h）； the administration frequencies were q12 h， q8 h. A total of 18 dosing regimens were designed. The probability of target attainment of %fT＞4MIC≥40% and Cmin≤27.5 mg/L were calculated respectively to optimize the dosing regimen. RESULTS For elderly patients with creatinine clearance （CLcr） ≤40 mL/min， when the minimum inhibitory concentration （MIC） was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous drip 0.5 h， q12 h”“ 1 g， intravenous injection， q12 h”. When the MIC was equaled to 2 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h”“ 1 g， intravenous drip 0.5 h， q12 h”. When the MIC was equaled to 4， 8 mg/L， the suggested dosing regimens were “1 g （or 2 g）， intravenous injection， q8 h”. For elderly patients with CLcr equal to 50 mL/min， when the MIC was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h“”1 g， intravenous injection， q12 h”. When the MIC was equal to 2， 4， 8 mg/L，the suggested dosing regimens were“0.5 g （or 1 g， or 2 g）， intravenous drip for 0.5 h， q8 h”. The appropriate dosing regimens of all the above protocols were above 96.6%. In the dosing regimen of “2 g，intravenous injection or intravenous drip 0.5 h， q8 h”， Cmin＞27.5 mg/L occurred in 40 times among the 1 000 times of simulation， indicating adverse reactions of the nervous system may occur. CONCLUSIONS For the elderly patients with renal insufficiency， the dosing regimen of meropenem should be adjusted accordingly with CLcr＝40 mL/min as the boundary， and the toxicity of nervous system should be considered at the same time. |
| 期刊： | 2023年第34卷第02期 |
| 作者： | 叶红波；宋洋洋；芮建中 |
| AUTHORS： | YE Hongbo，SONG Yangyang，RUI Jianzhong |
| 关键字： | 美罗培南；蒙特卡罗模拟；二房室；肾功能不全；老年患者 |
| KEYWORDS： | meropenem； Monte Carlo simulation； two- |
| 阅读数： | 161 次 |
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