应用蒙特卡洛模拟法优化艾沙康唑给药方案

目的根据药代动力学/药效学(PK/PD)理论,应用蒙特卡洛模拟评价艾沙康唑给药方案,为临床给药方案优化提供依据。方法结合艾沙康唑药动学及真菌药敏文献资料,采用水晶球软件,对50、100 mg 1次/d口服(po)给药及50、100、200、400 mg静脉给药(iv)共6种给药方案分别进行10 000次蒙特卡洛模拟,以达标概率(PTA)和累计反应分数(CFR)作为评价指标。结果 6种给药方案(50 mg po、100 mg po、50 mg ivgtt、100mg ivgtt、200 mg ivgtt、400 mg ivgtt)对白色念珠菌的CFR值分别为38.94%、72.42%、22.51%、59.19%、88.26%和99.49%,对烟曲霉菌的CFR值分别为30.62%、75.88%、15.49%、67.07%、86.16%和96.68%。结论艾沙康唑单日给药剂量达到200 mg及以上时,基本可以满足对大部分白色念珠菌和烟曲霉菌感染的治疗需要。

Using Monte Carlo simulation to optimize the dosage regimen of isavuconazonium

Objective To evaluate the dosage regimen of isavuconazonium ( ISA) by Monte Carlo simulation according to the pharmacokinetic/pharmacodynamic ( PK/PD) studies and to provide evidence for its optimization. Methods Based on pharmacokinetic and susceptibility data,six dosages of ISA were used,including 50 and 100 mg by oral method (po) and 50,100,200 and 400 mg by intravenous method (iv),once daily. The probability of target at-tainment ( PTA) and cumulative fraction of response ( CFR) were simulated using Crystal Ball software. Results The CFRs were 38. 94%, 72. 42%, 22. 51%, 59. 19%, 88. 26% and 99. 49% to C. albicans and 30. 62%, 75. 88%, 15. 491%,67. 07%,86. 16%,96. 68% to A. fumigates,at six dosage regimens of ISA respectively (50 mg po,100 mg po,50 mg ivgtt,100 mg ivgtt,200 mg ivgtt and 400 mg ivgtt) . Conclusion Strains of C. albicans and A. fumigatus can respond significantly to ISA (≥200 mg/d) .