In Vivo Comparison of the Pharmacodynamic Targets for Echinocandin Drugs against Candida Species
In Vivo Comparison of the Pharmacodynamic Targets for Echinocandin Drugs against Candida Species
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DOI：
10.1128/aac.01584-09
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发表时间：
2010-06-01
影响因子：
4.9
通讯作者：
Lepak, A.
中科院分区：
文献类型：
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作者：
Andes, D.;Diekema, D. J.;Lepak, A.
先前使用体内念珠菌病模型进行的药效学研究已经证明，24小时浓度-时间曲线下面积（AUC）/MIC是棘白菌素药物-反应关系的良好描述符。进一步研究了停滞终点的24小时AUC/MIC目标，确定了针对白色念珠菌的游离药物24小时AUC/MIC，并且对于两种棘白菌素，阿尼芬净和云母芬净是相似的。目前的研究扩展了对第三种棘白菌素（卡泊芬净）的研究，并比较了卡泊芬净与卡泊芬净之间的药效学靶点。白色念珠菌、光滑念珠菌和近平滑念珠菌。用6个C.白色念珠菌9株，白色念珠菌9株。glabrata和15 C.具有不同MIC的近平滑菌株（阿尼芬净，0.015至4.0 μ g/ml;卡泊芬净，0.03至4.0 μ g/ml;米卡芬净，0.008至1.0 μ g/ml）。疗效与MIC和24小时AUC/MIC密切相关。抗C.近平滑病需要更多的每种棘白菌素（mg/kg）。卡泊芬净对所有微生物的有效性所需的药物（mg/kg）少于其他两种药物。然而，当考虑游离药物浓度时，棘白菌素的24小时AUC/MIC目标相似，表明蛋白结合的相关性。C. parapsilosis（平均7只）和C. glabrata（平均7）显著低于C.白色念珠菌（平均20）。结果表明，目前的敏感性折点和考虑的生物物种在这些测定应重新探讨。
Previous pharmacodynamic studies using in vivo candidiasis models have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC is a good descriptor of the echinocandin exposure-response relationship. Further studies investigating the 24-h AUC/MIC target for a stasis endpoint identified free-drug 24-h AUC/MIC against Candida albicans and were similar for two echinocandins, anidulafungin and mica-fungin. The current studies expand investigation of a third echinocandin (caspofungin) and compare the pharmacodynamic target among C. albicans, Candida glabrata, and Candida parapsilosis. Treatment studies were conducted with six C. albicans, nine C. glabrata, and 15 C. parapsilosis strains with various MICs (anidulafungin, 0.015 to 4.0 mu g/ml; caspofungin, 0.03 to 4.0 mu g/ml; and micafungin, 0.008 to 1.0 mu g/ml). Efficacy was closely tied to MIC and the 24-h AUC/MIC. Therapy against C. parapsilosis required more of each echinocandin on a mg/kg basis. Caspofungin required less drug on a mg/kg basis for efficacy against all of the organisms than did the other two drugs. However, the 24-h AUC/MIC targets were similar among the echinocandins when free drug concentrations were considered, suggesting the relevance of protein binding. The targets for C. parapsilosis (mean, 7) and C. glabrata (mean, 7) were significantly lower than those for C. albicans (mean, 20) for each echinocandin. The results suggest that current susceptibility breakpoints and the consideration of organism species in these determinations should be reexplored.