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脂质体两性霉素B,安必素。

Liposomal amphotericin B, AmBisome.

作者信息

Hay R J

机构信息

United Medical School, Guys Hospital, London, U.K.

出版信息

J Infect. 1994 May;28 Suppl 1:35-43. doi: 10.1016/s0163-4453(94)95956-0.

Abstract

The unilamellar liposomal formulation of amphotericin B, AmBisome, is composed of hydrogenated soy phosphatidylcholine, distearoyl phosphatidylglycerol and cholesterol. Early studies of its efficacy in an open design showed that remissions could be induced in candidosis and aspergillosis and that doses of up to 5 mg/kg could be used. Adverse events were infrequent, with the main abnormality seen being hypokalaemia in about 18% of patients. Subsequent developments have extended this work. AmBisome has been used in two open studies of patients with invasive aspergillosis; in one of these remission was achieved in 77% of 17 patients with confirmed infection who had failed to respond to conventional amphotericin B. In AIDS patients with cryptococcosis AmBisome given for 6 weeks at 3 mg/kg daily produced mycological remission of meningitis in 67%. Other infections treated with the drug include zygomycete (mucormycosis) and Fusarium infections. AmBisome has also been used as preventative therapy in bone marrow transplant recipients and was found to reduce fungal colonisation rates. There were fewer systemic fungal infections in the treated versus placebo groups although this did not achieve statistical significance. Lack of renal and liver toxicity or anaemia has been confirmed in subsequent studies. In addition febrile reactions to the AmBisome are rare. The drug has also been used effectively in children, including infants, with systemic fungal infections. In visceral leishmaniasis patients, including HIV positive individuals, remissions have been obtained using drug regimens of 1-2 mg/kg of 2.1 days and 3 mg/kg for 10 days.

摘要

两性霉素B的单层脂质体制剂安必素由氢化大豆卵磷脂、二硬脂酰磷脂酰甘油和胆固醇组成。早期在开放设计中对其疗效的研究表明,念珠菌病和曲霉病可实现缓解,且可使用高达5mg/kg的剂量。不良事件很少见,主要异常表现为约18%的患者出现低钾血症。随后的进展扩展了这项工作。安必素已用于两项侵袭性曲霉病患者的开放研究;其中一项研究中,17例确诊感染且对传统两性霉素B无反应的患者中有77%实现了缓解。在患有隐球菌病的艾滋病患者中,每天3mg/kg给予安必素6周,67%的患者脑膜炎实现了真菌学缓解。用该药物治疗的其他感染包括接合菌(毛霉病)和镰刀菌感染。安必素也已用作骨髓移植受者的预防性治疗,发现可降低真菌定植率。治疗组与安慰剂组相比,系统性真菌感染较少,尽管这未达到统计学意义。后续研究证实无肾毒性、肝毒性或贫血。此外,对安必素的发热反应很少见。该药物也已有效地用于患有系统性真菌感染的儿童,包括婴儿。在内脏利什曼病患者,包括HIV阳性个体中已使用1 - 2mg/kg共2.1天和3mg/kg共10天的药物方案实现了缓解。

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