基于蒙特卡洛模拟法优化米诺环素的给药方案

Optimum Dosage Regimen of Minocycline Based on Monte Carlo Simulation

目的:利用蒙特卡洛模拟法计算米诺环素在不同给药剂量下(单剂量静滴50,100和200mg)AUC/ MIC值概率分布。方法:收集已发表的米诺环素的药动学资料和解脲脲原体对该抗生素的MIC分布数据,利用Crystal Ball软件模拟5 000个"患者"的治疗试验,求算出每个"患者"的AUC/MIC值及其概率分布,进而找出最佳治疗方案。结果:米诺环素在高、中、低3种给药剂量下均能取得较好的治疗效果,AUIC达到有效治疗指标(AUIC≥25 h)的概率分别为高(100%)、中(100%)和低(99.09%)。结论:蒙特卡洛模拟法把药动学和药效学结合起来,既考虑了不同个体对药物处置的差异性,又考虑了病原菌耐药性的差异,这样获得的给药方案将更合理,也更能提高临床治疗效果。

Objective： This study evaluated the AUC/MIC ratios for minocycline which was administered with different dosages against Ureaplasma urealyticum using a Monte Carlo simulation. Methods： Pharmacokinetic data and 49 MIC distributions against Ureaplasma urealyticum were obtained from the studies in healthy volunteers published in the literature. Monte Carlo simulation of 5 000 patients was done to attain the probability and frequency of each AUC/MIC ratio and the best dosage regiment was chosen. Results： 100%, 100% and 99.09% of the 5 000 patients treated with minocycline using the three dosage regiments attained a good pharmacodynamic target, respectively. Conclusion： Designing of dosage regimen based on Monte Carlo simulation is reasonable and valid, because this method has taken the differences between individuals into full account.