Gokhale P C, Barapatre R J, Advani S H, Kshirsagar N A, Pandya S K
Department of Pharmacology, Seth G.S. Medical College, Bombay, India.
J Antimicrob Chemother. 1993 Jul;32(1):133-9. doi: 10.1093/jac/32.1.133.
Amphotericin B incorporated into small unilamellar liposomes prepared from soya phosphatidylcholine and cholesterol in a molar ratio of 7:3 was administered to 12 patients with suspected or documented systemic fungal infection. Each patient received 0.1, 0.4 and 1.0 mg/kg dose of liposomal amphotericin B. Liposomal amphotericin B was well tolerated by these patients with no dose-limiting toxicity. Mild to moderate fever with rigors occurred in 3 patients after the higher doses. Peak plasma amphotericin B concentrations, measured by HPLC; were 0.747-1.429 mg/L and 24 h trough concentrations were 0.148-0.363 mg/L. The mean T1/2 beta of amphotericin B was 17.2 h with a mean volume of distribution of 2.285 L/kg. While these pharmacokinetic parameters obtained with this liposomal amphotericin B formulation are comparable to the values obtained after conventional amphotericin B therapy, they are strikingly different from values obtained by other workers using small unilamellar liposomes with either positive or negative charge. Yet in animal experiments the distribution of all formulations are comparable.
将两性霉素B包裹于由大豆磷脂酰胆碱和胆固醇按摩尔比7:3制备的小单层脂质体中，给予12例疑似或确诊为系统性真菌感染的患者。每位患者接受0.1、0.4和1.0mg/kg剂量的脂质体两性霉素B。这些患者对脂质体两性霉素B耐受性良好，无剂量限制性毒性。3例患者在接受较高剂量后出现轻度至中度寒战发热。通过高效液相色谱法测定，血浆两性霉素B峰值浓度为0.747 - 1.429mg/L，24小时谷浓度为0.148 - 0.363mg/L。两性霉素B的平均β半衰期为17.2小时，平均分布容积为2.285L/kg。虽然这种脂质体两性霉素B制剂获得的这些药代动力学参数与传统两性霉素B治疗后获得的值相当，但与其他研究人员使用带正电荷或负电荷的小单层脂质体获得的值显著不同。然而，在动物实验中，所有制剂的分布情况相当。
