Premaratne S, May M L, Nakasone C K, McNamara J J
Department of Radiology, Stonybrook University Hospital, New York 11794, USA.
J Surg Res. 1995 Oct;59(4):428-32. doi: 10.1006/jsre.1995.1186.
Using a prospective, randomized, controlled study, we tested the hypothesis that the initial administered dose of endotoxin determines its pharmacokinetics in a rhesus macaque septic shock model. Twelve adult male rhesus macaques, weighing 6 to 10 kg, were equally divided into two groups. The first group received a 20 mg/kg intravenous bolus of the gram-negative endotoxin. The second group received a bolus comparable to the concentration of endotoxin found in the plasma of the first group, 12 hr postendotoxin injection. Both groups were monitored for 12 hr and sacrificed. Plasma endotoxin concentrations were measured using the limulus amebocyte lysate assay and a pharmacokinetic model was applied to the concentration curves. Results of the pharmacokinetic evaluation revealed differences in half-life, clearance, and total apparent volume of distribution between the two groups of animals, suggesting that the changes in these parameters may have a biphasic pattern and may be related to the initial dose of endotoxin injected.
通过一项前瞻性、随机、对照研究，我们检验了以下假设：在恒河猴脓毒性休克模型中，内毒素的初始给药剂量决定其药代动力学。12只体重6至10千克的成年雄性恒河猴被平均分为两组。第一组静脉推注20毫克/千克的革兰氏阴性内毒素。第二组在注射内毒素12小时后接受与第一组血浆中内毒素浓度相当的推注。两组均监测12小时后处死。使用鲎试剂法测定血浆内毒素浓度，并将药代动力学模型应用于浓度曲线。药代动力学评估结果显示，两组动物在内毒素半衰期、清除率和总表观分布容积方面存在差异，这表明这些参数的变化可能呈双相模式，并且可能与注射的内毒素初始剂量有关。
