Optimization of Dosage Regimen of Rezafungin against Candida spp. Based on Pharmacokinetic/Pharmacodynamic Analysis

Jiuli Hu, Junhui Hu
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Abstract

Invasive candidiasis was the most common nosocomial fungal infection with high morbidity and mortality, which is mainly occurring in immunodeficiency and critical patients. Echinocandins were recommended as first-line drugs for the treatment and prevention of invasive candidiasis. In our study, we aimed to optimize the dosage of Rezafungin against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of rezafungin and the MIC distribution of Candida spp. on rezafungin. Monte Carlo simulation was used to calculate probability of target attainment and a cumulative fraction of response to assess the best dosing regimen. The optimal dosage regimen for C. albicans and C. glabrata was 50 mg IV, and the optimal dosage regimen for C. parapsilosis was 100 mg IV. Lastly, rezafungin has an excellent antifungal effect on C. albicans, C. glabrata and C. parapsilosis.
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基于药代动力学/药效学分析的热复宁抗念珠菌给药方案优化
侵袭性念珠菌病是最常见的医院真菌感染,发病率和死亡率高,主要发生在免疫缺陷和危重患者中。棘白菌素被推荐为治疗和预防侵袭性念珠菌病的一线药物。本研究旨在通过药代动力学/药效学(PK/PD)分析,优化Rezafungin抗念珠菌的剂量。我们收集了热复宁的药动学参数和念珠菌在热复宁上的MIC分布的已发表资料。采用蒙特卡罗模拟计算达到目标的概率和累积反应分数,以评估最佳给药方案。对白色念珠菌、光秃念珠菌的最佳给药方案为50 mg IV,对副枯枝念珠菌的最佳给药方案为100 mg IV。最后,热复宁对白色念珠菌、光秃念珠菌、副枯枝念珠菌均有较好的抗真菌效果。
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