Safety and pharmacokinetics of intravenous anidulafungin in children with neutropenia at high risk for invasive fungal infections
Safety and pharmacokinetics of intravenous anidulafungin in children with neutropenia at high risk for invasive fungal infections
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DOI：
10.1128/aac.50.2.632-638.2006
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发表时间：
2006-02-01
影响因子：
4.9
通讯作者：
Walsh, TJ
中科院分区：
文献类型：
--
作者：
Benjamin, DK;Driscoll, T;Walsh, TJ
阿尼芬净是一种棘白菌素，具有对抗念珠菌属和曲霉属的活性。正在研究的成人剂量为食管念珠菌病 50 毫克/天，侵袭性念珠菌病和曲霉菌病 100 毫克/天。然而，人们对阿尼芬净在儿童中的安全性和药代动力学知之甚少。因此，对中性粒细胞减少症儿科患者进行了一项多中心剂量递增研究。患者被分为两个年龄组（2至11岁和12至17岁），并被分入连续组，接受0.75或1.5毫克/公斤体重/天的剂量。在第一剂和第五剂后采集血样。对血浆中的阿尼芬净进行测定，并测定药代动力学参数。使用美国国家癌症研究所 (NCI) 通用毒性标准评估安全性。测定了 12 名患者每个剂量（0.75 mg/kg/天或 1.5 mg/kg/天）的药代动力学参数。不同年龄组患者的浓度和药物暴露量相似，并且体重调整后的清除率在不同年龄组中是一致的。没有观察到与药物相关的严重不良事件。一名患者出现发烧（NCI 毒性等级为 3 级），一名患者出现面部红斑，但通过减慢输注速度即可缓解。阿尼芬净在儿童患者中耐受性良好，可根据体重确定剂量。接受 0.75 mg/kg/天或 1.5 mg/kg/天的儿童患者的阿尼芬净浓度分布与分别接受 50 或 100 mg/天的成人患者的浓度分布相似。
Anidulafungin is an echinocandin with activity against Candida species and Aspergillus species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children. A multicenter, ascending-dosage study of neutropenic pediatric patients was therefore conducted. Patients were divided into two age cohorts (2 to 11 years and 12 to 17 years) and were enrolled into sequential groups to receive 0.75 or 1.5 mg/kg of body weight/day. Blood samples were obtained following the first and fifth doses. Anidulafungin was assayed in plasma, and pharmacokinetic parameters were determined. Safety was assessed using National Cancer Institute (NCI) common toxicity criteria. Pharmacokinetic parameters were determined for 12 patients at each dosage (0.75 mg/kg/day or 1.5 mg/kg/day). Concentrations and drug exposures were similar for patients between age cohorts, and weight-adjusted clearance was consistent across age. No drug-related serious adverse events were observed. One patient had fever (NCI toxicity grade of 3), and one patient had facial erythema, which resolved with slowing the infusion rate. Anidulafungin in pediatric patients was well tolerated and can be dosed based on body weight. Pediatric patients receiving 0.75 mg/kg/day or 1.5 mg/kg/day have anidulafungin concentration profiles similar to those of adult patients receiving 50 or 100 mg/day, respectively.