Basic Medical College, Tianjin Medical University, 22# Qixiangtai Road, Heping District, Tianjin 300070, China.
Department of Pharmacy, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin 300192, China.
Int J Antimicrob Agents. 2015 Dec;46(6):631-41. doi: 10.1016/j.ijantimicag.2015.08.009. Epub 2015 Sep 21.
This study aimed to investigate the cumulative fraction of response of various echinocandin (caspofungin, micafungin and anidulafungin) dosing regimens against Candida spp. in paediatric patients with invasive fungal infections (IFIs). Monte Carlo simulations were performed using previously published pharmacokinetic parameters and pharmacodynamic data to evaluate the ability of each echinocandin regimen in terms of fAUC/MIC (free drug area under the concentration-time curve/minimum inhibition concentration ratio) targets of caspofungin, micafungin and anidulafungin. Pharmacodynamic targets were attained in paediatric patients by both caspofungin regimens as well as by a high micafungin dosing regimens against Candida albicans and Candida glabrata. However, the results for anidulafungin suggested that the dosing regimens recommended were not optimal for paediatric patients. In addition, the predicted efficacy of all of the echinocandins against Candida parapsilosis was low. This is the first study to assess caspofungin, micafungin and anidulafungin therapy using Monte Carlo simulation. These results rationalise and optimise the dosage regimens of caspofungin, micafungin and anidulafungin against C. albicans, C. glabrata and C. parapsilosis for paediatric patients with IFIs.
本研究旨在探讨不同棘白菌素（卡泊芬净、米卡芬净和阿尼芬净）给药方案对侵袭性真菌感染（IFI）患儿的累积反应率。使用先前发表的药代动力学参数和药效学数据进行蒙特卡罗模拟，以评估每种棘白菌素方案在卡泊芬净、米卡芬净和阿尼芬净的 fAUC/MIC（游离药物浓度时间曲线下面积/最小抑制浓度比值）目标方面的能力。卡泊芬净的两种给药方案以及高剂量米卡芬净方案均可达到儿科患者的药效学目标，适用于治疗白色念珠菌和近平滑念珠菌。然而，阿尼芬净的结果表明，推荐的给药方案对儿科患者并不理想。此外，所有棘白菌素对近平滑念珠菌的预测疗效均较低。这是第一项使用蒙特卡罗模拟评估卡泊芬净、米卡芬净和阿尼芬净治疗的研究。这些结果使卡泊芬净、米卡芬净和阿尼芬净针对IFI 患儿的白色念珠菌、近平滑念珠菌和光滑念珠菌的剂量方案合理化和优化。
