Abstract

Background

We conducted a prospective study in ICU patients of two tertiary hospitals in order to determine basic pharmacokinetic (PK) parameters, associated variation and target attainment rates for anidulafungin, micafungin and caspofungin.

Methods

Serum samples from patients treated for 7 days with the standard doses of anidulafungin (N = 13), micafungin (N = 14) or caspofungin (N = 7) were analysed by validated chromatographic methods. PK parameters determined with non-compartmental analysis were correlated with demographic, laboratory and disease severity characteristics. The percentages of patients attaining drug exposures described in the summary of product characteristics (SmPC) documents and preclinical PK/PD targets for stasis were estimated.

Results

The median (range) AUC₂₄ was 101.46 (54.95–274.15) mg·h/L for anidulafungin, 79.35 (28.00–149.30) mg·h/L for micafungin and 48.46 (19.44–103.69) mg·h/L for caspofungin. The interindividual variability of anidulafungin, micafungin and caspofungin AUC₂₄ was 46%–58%, attributed mainly to variability in volume of distribution (V), clearance (CL) and in both V and CL, respectively. Significant correlations were found between anidulafungin AUC₂₄ and BMI (r_s = −0.670, P = 0.012) and liver enzymes (r_s = 0.572–0.665, P = 0.013–0.041) and between caspofungin C_min and transaminase levels (r_s = −0.775 to −0.786, P = 0.036–0.041). Less than 50% of our patients attained the corresponding SmPC median AUC₂₄s and none of the patients attained the PK/PD targets for Candida albicans and Candida parapsilosis.

Conclusions

Anidulafungin exposure in ICU patients was comparable with that reported in non-ICU patients and in healthy volunteers. Micafungin exposure was comparable to that of other patients but ∼30% lower than that in healthy volunteers, whereas caspofungin exposure was rather low (∼50% lower than in healthy volunteers). Larger interindividual variability (50%–60%) was recorded in ICU patients compared with other groups for all three echinocandins.

中文翻译：

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三种棘皮and苷在ICU患者中的比较药代动力学。

摘要

背景

我们对两家三级医院的ICU患者进行了一项前瞻性研究，以确定阿尼芬净，米卡芬净和卡泊芬净的基本药代动力学（PK）参数，相关变异和目标达到率。

方法

从患者的血清样品治疗的7天与标准剂量的阿尼芬净（Ñ  = 净，米卡芬净（13）ñ  =  14）或卡泊芬净（ñ  =  7）通过验证的色谱法进行了分析。非房室分析确定的PK参数与人口统计学，实验室和疾病严重程度特征相关。估算了产品特征（SmPC）文件摘要和临床前PK / PD停滞靶点中描述的获得药物暴露的患者百分比。

结果

阿地芬净的中位（范围）AUC _{2 4}为101.46（54.95–274.15）mg·h / L，米卡芬净为79.35（28.00–149.30）mg·h / L和卡泊芬净为48.46（19.44–103.69）mg·h / L 。阿尼芬净，米卡芬净和卡泊芬净AUC ₂₄的个体间差异为46％–58％，主要归因于分布体积（V），清除率（CL）以及V和CL的差异。发现阿尼芬净AUC ₂₄和BMI（r _s  =  -0.670，P  =  0.012）和肝酶（r _s  =  0.572–0.665，P  = 0.013–0.041）和卡泊芬净C _min和转氨酶水平之间（r _s  =  -0.775至-0.786，P  =  0.036–0.041）。我们不到50％的患者达到了相应的SmPC中位数AUC ₂₄ s，并且没有患者达到白色念珠菌和副念珠菌的PK / PD目标。

结论

ICU患者的阿尼芬净暴露与非ICU患者和健康志愿者中报道的相当。米卡芬净暴露与其他患者相当，但比健康志愿者低约30％，而卡泊芬净暴露则低（比健康志愿者低约50％）。与所有其他三种棘球oc素组相比，ICU患者的个体间差异更大（50％–60％）。