Pharmacokinetics of an elevated dosage of micafungin in premature neonates.
Pharmacokinetics of an elevated dosage of micafungin in premature neonates.
复制标题
DOI：
10.1097/inf.0b013e3181910e2d
复制
发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Benjamin DK Jr
中科院分区：
文献类型：
--
作者：
Smith PB;Walsh TJ;Hope W;Arrieta A;Takada A;Kovanda LL;Kearns GL;Kaufman D;Sawamoto T;Buell DN;Benjamin DK Jr
确定新生儿抗真菌药物的安全性和药代动力学非常重要。先前在新生儿中进行的米卡芬净单次给药药代动力学研究表明，由于新生儿中米卡芬净的表观血浆清除率增加，因此0.75 - 3 mg/kg剂量产生的米卡芬净血浆浓度低于老年患者。本研究的主要目的是评估米卡芬净剂量增加（15 mg/kg/天）的安全性和药代动力学。一项在12名出生时间> 48小时的疑似全身性感染早产儿中进行的重复剂量、开放标签、静脉注射米卡芬净的药代动力学和安全性试验新生儿接受15 mg/kg/天米卡芬净给药5天。相对于第四次或第五次给药采集血样。通过检查血浆曲线下面积评估全身暴露量。新生儿的中位出生体重和胎龄分别为775 g和27周。未检测到与米卡芬净相关的不良事件。队列的平均曲线下面积和清除率分别为437.5 μg · h/mL和0.575 mL/min/kg。新生儿的计算清除率和分布容积大于年龄较大的儿童和成人。这些数据表明，早产儿中15 mg/kg剂量相当于成人中约5 mg/kg的暴露量。未观察到与米卡芬净相关的不良事件。
Determining the safety and pharmacokinetics of antifungal agents in neonates is important. A previous single-dose pharmacokinetic study of micafungin in neonates demonstrated that doses of 0.75 to 3 mg/kg produced lower plasma micafungin concentrations than in older patients because of increased apparent plasma clearance of micafungin in neonates. The primary objective of this study was to assess the safety and pharmacokinetics of an increased (15 mg/kg/day) dose of micafungin. A repeated dose, open-label pharmacokinetic and safety trial of intravenous micafungin in 12 preterm neonates > 48 hours of life with suspected systemic infections. Neonates received 15 mg/kg/day of micafungin for 5 days. Blood samples were drawn relative to either the fourth or fifth dose. Systemic exposure was assessed by examination of the plasma area under the curve. The median birth weight and gestational age of the neonates were 775 g and 27 weeks, respectively. No adverse events related to micafungin were detected. The mean area under the curve and clearance for the cohort was 437.5 μg · h/mL and 0.575 mL/min/kg, respectively. The calculated clearance and volume of distribution for neonates was greater than that observed in older children and adults. These data suggest that 15 mg/kg dosing in premature neonates corresponds to an exposure of approximately 5 mg/kg in adults. No adverse events related to micafungin were observed.