Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis
Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis
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DOI：
10.1093/jac/dkw568
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发表时间：
2017-05-01
影响因子：
5.2
通讯作者：
Montravers, P.
中科院分区：
文献类型：
--
作者：
Dupont, H.;Massias, L.;Montravers, P.
背景资料：只有有限的药代动力学数据可用于阿尼芬净在ICU患者，特别是在严重的腹腔内感染（IAI）治疗的患者。方法：这是一个前瞻性的多中心观察性研究在ICU患者疑似酵母IAI。所有患者均接受200 mg阿尼芬净静脉负荷剂量，随后为100 mg/天。在第1天和第5天之间采集13份血样用于药代动力学分析。通过HPLC-tandemMS方法分析样品。结果：14名患者中位年龄（IQR）为62岁（48-70），平均BMI为30.5 kg/m2，来自三个中心; 57.1%为女性。他们的中位数（IQR）SAPS 2评分为54（45-67），中位数（IQR）SOFA评分为8（7-12）。6例社区获得性IAI患者和8例医院获得性IAI患者被纳入。分离出12株酵母菌：6株白色念珠菌、2株光滑念珠菌、2株热带念珠菌、1株近平滑念珠菌和1株克柔念珠菌。药代动力学参数如下[平均值（%变异系数）]：C-max（mg/L）= 6.0（29%）; T-max（h）= 1.6（25.8%）; C-min（mg/L）= 3.2（36.8%）; AUC（0-24）（mg.h/L）= 88.9（38.6%）; t（1/2）（h）= 42.1（68.2%）; CL（L/h）= 1.2（42.3%）; V（L）= 72.8（87.8%）。二室模型最好地描述了阿尼芬净浓度的人口potentiometricstudy.Conclusions：阿尼芬净在重症ICU患者复杂的IAI的药代动力学参数是类似的文献中观察到的。然而，在本研究中观察到V增加和t（1/2）延长。（EudraCT编号2010-018695-25）
Background: Only limited pharmacokinetic data are available for anidulafungin in ICU patients, especially in patients treated for severe intra-abdominal infection (IAI).Methods: This was a prospective multicentre observational study in ICU patients with suspected yeast IAI. All patients received an intravenous loading dose of 200mg of anidulafungin, followed by 100 mg/day. Thirteen blood samples were drawn between day 1 and day 5 for pharmacokinetic analysis. Samples were analysed by an HPLC-tandemMS method. Demographics and SAPS2 and SOFA scores were recorded.Results: Fourteen patients with a median age (IQR) of 62 years (48-70) and with a mean BMI of 30.5 kg/m(2) were included from three centres; 57.1% were women. Their median (IQR) SAPS2 score was 54 (45-67) and their median (IQR) SOFA score was 8 (7-12). Six patients with community-acquired IAI and eight patients with nosocomial-acquired IAI were included. Twelve yeasts were isolated: six Candida albicans, two Candida glabrata, two Candida tropicalis, one Candida parapsilosis and one Candida krusei. Pharmacokinetic parameters were as follows [ mean (% coefficient of variation)]: C-max (mg/L) = 6.0 (29%); T-max (h) = 1.6 (25.8%); C-min (mg/L) = 3.2 (36.8%); AUC(0-24) (mg.h/L) = 88.9 (38.6%); t(1/2) (h) = 42.1 (68.2%); CL (L/h) = 1.2 (42.3%); and V (L) = 72.8 (87.8%). A two-compartment model best described the anidulafungin concentrations in the population pharmacokinetic study.Conclusions: The pharmacokinetic parameters of anidulafungin in critically ill ICU patients with complicated IAI are similar to those observed in the literature. However, an increased V and a longer t(1/2) were observed in this study. (EudraCT No. 2010-018695-25)