MULTIPLE DOSE STUDY OF LIPOSOMAL AMIKACIN IN HIV SEROPOTISTIVE PATIENTS

本方案的目的是确定安全性和药代动力学 Mikasome是一种氨基糖苷类抗生素的脂质体制剂， 阿米卡星，当在多剂量方案中给予时。研究是否 在艾滋病毒阳性志愿者中进行，因为这是目标之一， 使用该研究药物的人群， 有效治疗鸟分枝杆菌复合体（MAC）。非 临床和早期人类数据表明， 阿米卡星可能具有实质上不同的药代动力学，并且 因此，与 其他配方。研究设计为平行组给药 递增研究，每例受试者每日输注 阿米卡星脂质体连续给药7天。密集 在首次和末次输注时进行药代动力学采样 几天，几个星期后。对受试者进行密切监测 毒性的体征和症状，尤其是肾毒性。 药代动力学参数通过标准房室模型和 非房室方法。

The goal of this protocol is to define the safety and pharmacokinetics of Mikasome, a liposomal formulation of the aminoglycoside antibiotic amikacin, when given in multiple dose regime. The study is being carried out in HIV-positive volunteers, since this is one of the target populations for the use of this investigational agent which may be efficacious in the treatment of Mycobacterium Avium Complex (MAC). Non- clinical and early human data suggest that the liposomal formulation of amikacin may have substantially different pharmacokinetics, and therefore possible differences in efficacy and toxicity, compared with other formulations. The study design is a parallel group dose escalation study, with each subject receiving a daily infusion of liposomal amikacin for seven consecutive days. Intensive pharmacokinetic sampling is carried out on the first and last infusion days, and for several weeks afterwards. Subjects are monitored closely for signs and symptoms of toxicity, expecially renal toxicity. Pharmacokinetic parameters are analyzed by standard compartmental and non-compartmental methods.