药动学模型联合蒙特卡罗模拟优化老年类鼻疽患者抗菌药物给药方案

Optimization of Antimicrobial Administration in Elderly Patients with Melioidosis by Pharmacokinetic model combined with Monte Carlo simulation

关键词:  鼻疽  药动学  蒙特卡罗  美罗培南  用药方案  优化

Key words:  melioidosis  pharmacokinetic  Monte Carlo  meropenem  medication regimen  optimization

摘要:

目的 通过药动学模型联合蒙特卡罗模拟来完善老年类鼻疽患者抗菌药物的用药方案。方法 以美罗培南的药动学/药效学模型为基础，通过使用蒙特卡罗模拟法，模拟各种不同剂量美罗培南的临床用药方法，根据模拟结果明确最为理想的给药方式。结果 经过实验数据发现，初步预测AUC_{0-24 h}/MIC>400的百分比随着美罗培南剂量的增大而上升。当MIC的值为0.5 mg·L^–1，且美罗培南的使用剂量为25 mg·kg^–1·d^–1时，AUC_{0-24 h}/MIC>400的比例为99.43%。而MIC的值为1 mg·L^–1，且美罗培南的剂量为35 mg·kg^–1·d^–1时，AUC_{0-24 h}/MIC>400的比例为97.57%。当MIC值≥2 mg·L^–1时，美罗培南的剂量均无法满足AUC_{0-24 h}/MIC>400标准。结论 当MIC达到0.5 mg·L^–1时，临床使用美罗培南的给药剂量应> 25 mg·kg^–1·d^–1，而当MIC达到1 mg·L^–1时，美罗培南的使用剂量应>35 mg·kg^–1·d^–1。

Abstract:

OBJECTIVE To improve the medication regimen of antibiotics in elderly patients with melioidosis through pharmacokinetic model combined with Monte Carlo simulation. METHODS Based on the pharmacokinetic/pharmacodynamic model of meropenem, the Monte Carlo simulation was used to simulate the clinical drug use methods of various doses of meropenem, and the ideal drug delivery method was determined according to the simulation result. RESULTS The experimental data showed that the percentage of AUC_0-24/MIC>400 increased with the increase of meropenem dose. When the MIC value was 0.5 mg·L^-1 and the dosage of meropenem was 25 mg·kg^-1·d^-1, the proportion of AUC_0-24/MIC>400 was 99.43%. When the MIC value was 1 mg·L^-1 and the dose of meropenem was 35 mg·kg^-1·d^-1, the ratio of AUC_0-24/MIC>400 was 97.57%. When the MIC value was ≥ 2 mg·L^-1, the dose of meropenem could not meet the AUC_0-24/MIC>400 standard. CONCLUSION When the MIC reaches 0.5 mg·L^-1, the dosage of meropenem for clinical use should >25 mg·kg^-1·d^-1, while when the MIC reaches 1 mg·L^-1, the dosage of meropenem should be >35 mg·kg^-1·d^-1.