白色念珠菌
两性霉素B
白色体
药效学
最小抑制浓度
药代动力学
两性霉素B脱氧胆酸盐
脑膜脑炎
分布(数学)
药理学
微生物学
生物
免疫学
抗真菌
抗生素
数学分析
卡斯波芬金
数学
作者
Andreas H. Groll,Neelam Giri,Vidmantas Petraitis,Rūta Petraitienė,Myrna Candelario,John Bacher,Stephen C. Piscitelli,Thomas J. Walsh
摘要
The central nervous system (CNS) distribution and antifungal efficacy of all 4 approved formulations of amphotericin B (AmB) were investigated in a rabbit model of hematogenous Candida albicans meningoencephalitis. Treatment with AmB deoxycholate (1 mg/kg/day) or liposomal AmB (5 mg/kg/day) yielded the highest peak plasma concentration (C(max)), area under concentration versus time curve from zero to 24 h (AUC(0-24)), and time during dosing level tau Ttau>minimum inhibitory complex (MIC) values and led to complete eradication of C. albicans from brain tissue (P<.05 vs. untreated controls). By comparison, AmB colloidal dispersion and AmB lipid complex (5 mg/kg/day each) were only partially effective (not significant vs. untreated controls). There was a strong correlation of C(max), AUC(0-24), C(max)/MIC, AUC(0-24)/MIC, and Ttau>MIC with clearance of C. albicans from brain tissue (P=.0002). Although pharmacodynamic parameters derived from the MIC of free AmB were highly predictive of antifungal efficacy, parameters derived from MICs of individual formulations were not predictive. AmB deoxycholate and liposomal AmB had the greatest antifungal efficacy. This activity was concentration and time dependent.
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