Li Yanjun, Nguyen M Hong, Schmidt Stephan, Zhong Li, Derendorf Hartmut, Clancy Cornelius J
Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL, USA.
Int J Antimicrob Agents. 2009 Sep;34(3):240-5. doi: 10.1016/j.ijantimicag.2009.02.006. Epub 2009 Mar 31.
Using dynamic time-kill experiments with changing voriconazole concentrations, it was demonstrated that Candida albicans ATCC 90029 as well as Candida glabrata and Candida parapsilosis clinical isolates (two each) were significantly inhibited by starting concentrations of 4x and 16x the minimum inhibitory concentration (MIC) but not 1x MIC. Time-kill data were accurately fitted using a sigmoidal E(max) model. Pharmacokinetic (PK) parameters from human data sets were used in the model to simulate kill curves for typical treatment regimens. Simulated curves predicted that voriconazole would exert prolonged fungistatic activity against all five isolates. For three isolates, reductions from starting inocula over 60 h were predicted to exceed 2 log. Combining in vitro time-kill data with existing in vivo PK data might serve as an alternative to animal studies in defining optimal antifungal regimens.
通过使用不同伏立康唑浓度的动态时间杀菌实验表明，白色念珠菌ATCC 90029以及光滑念珠菌和近平滑念珠菌临床分离株（各两株）在起始浓度为最低抑菌浓度（MIC）的4倍和16倍时受到显著抑制，但在1倍MIC时未受到抑制。时间杀菌数据使用S型E(max)模型进行了精确拟合。该模型使用来自人体数据集的药代动力学（PK）参数来模拟典型治疗方案的杀菌曲线。模拟曲线预测伏立康唑对所有五株分离株均具有延长的抑菌活性。对于三株分离株，预计在60小时内起始接种量的减少将超过2个对数。将体外时间杀菌数据与现有的体内PK数据相结合，可能作为定义最佳抗真菌方案的动物研究的替代方法。
