Sundelof J G, Hajdu R, Cleare W J, Onishi J, Kropp H
Merck Institute for Therapeutic Research, Rahway, New Jersey 07065.
Antimicrob Agents Chemother. 1992 Mar;36(3):607-10. doi: 10.1128/AAC.36.3.607.
The time course of plasma drug levels and urinary recovery for two lipopeptide antifungal antibiotics, L-671,329 and cilofungin, were measured in male rhesus monkeys (Macaca mulatta) and in female DBA/2 mice. The antibiotics were administered intravenously at 10 mg/kg of body weight in phosphate-buffered saline-26% polyethylene glycol for the rhesus monkeys and in 5% dimethyl sulfoxide for the mice. Plasma and urine drug concentrations were determined by high-pressure liquid chromatography and/or a microbiological assay versus Aspergillus niger, and pharmacokinetic parameters were determined for both species. In each of the two rhesus crossover tests as well as in the mouse studies, the pharmacokinetics of the two compounds were similar; however, a marked difference was evident between species. The half-lives of L-671,329 and cilofungin in plasma were 39 and 34 min in the mice and averaged 1.8 and 2 h in the rhesus monkeys, respectively. In mice and rhesus monkeys, urinary recovery was less than 4% for both compounds.
在雄性恒河猴（猕猴属）和雌性DBA/2小鼠中测定了两种脂肽类抗真菌抗生素L-671,329和西洛芬净的血浆药物水平和尿液回收率的时间进程。对于恒河猴，抗生素以10 mg/kg体重静脉注射于磷酸盐缓冲盐水-26%聚乙二醇中；对于小鼠，抗生素以10 mg/kg体重静脉注射于5%二甲基亚砜中。通过高压液相色谱法和/或针对黑曲霉的微生物测定法测定血浆和尿液中的药物浓度，并确定了两个物种的药代动力学参数。在两项恒河猴交叉试验以及小鼠研究中，两种化合物的药代动力学相似；然而，不同物种之间存在明显差异。L-671,329和西洛芬净在小鼠血浆中的半衰期分别为39分钟和34分钟，在恒河猴中平均分别为1.8小时和2小时。在小鼠和恒河猴中，两种化合物的尿液回收率均低于4%。
