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[为什么米卡芬净可能是儿科患者的首选药物?]

[Why might micafungin be the drug of choice in pediatric patients?].

作者信息

Ramos Amador José Tomás, Prieto Tato Luis, Guillén Martín Sara

机构信息

Unidad de Enfermedades Infecciosas, Servicio de Pediatría, Hospital Universitario de Getafe, Madrid, España.

出版信息

Enferm Infecc Microbiol Clin. 2011 Mar;29 Suppl 2:23-8. doi: 10.1016/S0213-005X(11)70005-2.

Abstract

Micafungin is an echinocandin approved by the European Medicines Evaluation Agency for the treatment of invasive candidiasis in children, including premature infants born before 29 weeks of pregnancy, and as prophylaxis in children undergoing hematopoietic stem-cell transplantation or patients at risk of prolonged neutropenia. This drug has good activity in several Candida spp., including those resistant to fluconazole. Although micafungin is active against Aspergillus spp., it has been used mainly in combination therapy for invasive aspergillosis. There is ample information on the use of micafungin in children, including neonates, and this drug is the only echinocandin approved for use in infants aged less than 3 months. The efficacy, pharmacokinetics and safety of micafungin have been evaluated in phase II and III clinical trials in children, in which its efficacy and safety were demonstrated in comparison with liposomal amphotericin B and fluconazole. The pharmacokinetic profile of micafungin in children allows once daily intravenous administration, with greater clearance than in adults, and consequently pediatric doses are relatively higher. The most appropriate dose in children weighing less than 40 kg is 2 mg/kg/day in the treatment of invasive candidiasis and 1 mg/kg/day as prophylaxis in children undergoing hematopoietic stem-cell transplantation. Doses in neonates should be higher. In premature infants, the most appropriate doses to achieve levels in the brain parenchyma are 7 mg/kg/day and 10 mg/kg/day in those weighing more and less than 1,000 g, respectively. Micafungin has few drug-drug interactions and an acceptable safety profile. Withdrawal of this drug due to adverse effects is rare, although transaminase monitoring is recommended during treatment, as well as evaluation of the risk-benefit balance in patients with liver disease or concomitant administration of hepatotoxic drugs.

摘要

米卡芬净是一种棘白菌素,已获欧洲药品评估局批准,用于治疗儿童侵袭性念珠菌病,包括妊娠29周前出生的早产儿,也用于造血干细胞移植儿童或有长期中性粒细胞减少风险患者的预防治疗。该药物对多种念珠菌属具有良好活性,包括对氟康唑耐药的菌株。虽然米卡芬净对曲霉属有活性,但主要用于侵袭性曲霉病的联合治疗。关于米卡芬净在包括新生儿在内的儿童中的使用有大量信息,且该药物是唯一被批准用于3个月以下婴儿的棘白菌素。米卡芬净的疗效、药代动力学和安全性已在儿童的II期和III期临床试验中进行了评估,试验中将其与脂质体两性霉素B和氟康唑比较,证明了其疗效和安全性。米卡芬净在儿童中的药代动力学特征允许每日一次静脉给药,清除率高于成人,因此儿童剂量相对较高。体重小于40kg的儿童治疗侵袭性念珠菌病的最适宜剂量为2mg/kg/天,造血干细胞移植儿童预防治疗的最适宜剂量为1mg/kg/天。新生儿剂量应更高。在早产儿中,体重超过和低于1000g的婴儿,要在脑实质中达到相应水平的最适宜剂量分别为7mg/kg/天和10mg/kg/天。米卡芬净的药物相互作用较少,安全性可接受。因不良反应而停用该药物的情况很少见,不过治疗期间建议监测转氨酶,同时对肝病患者或同时使用肝毒性药物的患者评估风险效益平衡。

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