蒙特卡洛模拟优化不同地区肾移植受者伏立康唑静脉滴注治疗侵袭性烟曲霉菌感染的给药方案

Application of Monte Carlo Simulation on Optimizing Dosage Regimens of Intravenous Drip of Voriconazole Against Invasive Aspergillus Fumigatus Infection in Renal Transplant Recipients from Different Regions of China

目的应用蒙特卡洛模拟优化不同地区肾移植受者伏立康唑静脉滴注治疗侵袭性烟曲霉菌感染的给药方案。方法查阅伏立康唑对不同地区(东部、东南部、北部和西部)烟曲霉菌的最低抑菌浓度(MIC)及其药动学资料,采用Crystal Ball软件模拟5 000例次后得到治疗靶标f·AUC_(24h)/MIC> 25的达标概率(PTA),并推荐最佳给药方案。结果当静脉滴注每12 h 350 mg的伏立康唑应用于东部、北部和西部地区的肾移植受者时,其对烟曲霉菌的PTA值大于90%,此时为最佳给药方案;而对于东南部地区的肾移植受者,即使静脉滴注每12 h 400 mg的伏立康唑,其对烟曲霉菌的PTA值亦小于90%。结论伏立康唑静脉滴注应用于我国不同地区肾移植受者治疗侵袭性烟曲霉菌感染时的最佳给药方案存在差异,对于东南部地区的肾移植受者,常规剂量静脉滴注伏立康唑无法达到满意的治疗效果。

Objective To optimize dosage regimens of intravenous injection of voriconazole against invasive Aspergillus fumigatus infection in renal transplant recipients from different regions of China by using Monte Carlo simulation. Methods The minimum inhibitory con-centration（MIC） and pharmacokinetics of voriconazole against Aspergillus fumigatus in different regions of China （eastern, southeastern, northern and western） were investigated. Five thousand times Monte Carlo simulation were conducted to obtain the probability of target attainment（PTA） of the target f· AUC24 b 〉 25 by using Crystal Ball software and to recommend dosage regimens. Results For renal transplant recipients from eastern, northern, and western regions of China, the PTA for Aspergillus fumigatus was more than 90% when intravenous drip of voriconazole 350 mg/q 12 h, which was the best dosage regimen. However, for renal transplant recipients from south-eastern region of China, the PTA for Aspergillus fumigatus was less than 90% even after intravenous drip of voriconazole 400 mg/q 12 h. Conclusion The optimal regimens of intravenous drip of voriconazole against invasive Aspergillus fumigatus infection were different for renal transplant recipients from different regions of China. Conventional dose of intravenous drip of voriconazole is not enough for renal transplant recipients from southeastern region of China.