Shah A K, Sawchuk R J
Department of Pharmaceutics, University of Minnesota, Minneapolis 55455.
Biopharm Drug Dispos. 1991 Aug-Sep;12(6):457-66. doi: 10.1002/bdd.2510120607.
The effect of Intralipid co-administration on the pharmacokinetics of cyclosporine (CyA) was studied in NZW rabbits. A single intravenous bolus dose of CyA (10 mg kg-1) mixed with 3 ml of Intralipid was administered to rabbits (n = 4). Control animals (n = 4) received the same dose of CyA without Intralipid. Serial blood samples were collected up to 12 h after the administration of CyA. Concentrations of CyA in plasma were analyzed using a HPLC method. The terminal elimination half-life (t1/2) of CyA was significantly lower with Intralipid administration (191 +/- 25 min) than control (298 +/- 59 min). The total body clearance (ClTOT) and volume of distribution (Vdss) of CyA was reduced by approximately 65-70 per cent with Intralipid administration compared to control. The free fraction of CyA in plasma with and without Intralipid administration was estimated to be 0.05 +/- 0.01 and 0.17 +/- 0.06, respectively. Co-administration of Intralipid with CyA decreased both the ClTOT and Vdss resulting in a rapid elimination, i.e., decrease in a t1/2 of CyA from the body.
在新西兰白兔中研究了脂质乳剂联合给药对环孢素（CyA）药代动力学的影响。给兔子（n = 4）静脉注射单次大剂量的CyA（10 mg kg-1），并与3 ml脂质乳剂混合。对照动物（n = 4）接受相同剂量的CyA但不添加脂质乳剂。在注射CyA后12小时内连续采集血样。使用高效液相色谱法分析血浆中CyA的浓度。与对照组相比，脂质乳剂给药后CyA的终末消除半衰期（t1/2）显著降低（191 +/- 25分钟），而对照组为（298 +/- 59分钟）。与对照组相比，脂质乳剂给药使CyA的总体清除率（ClTOT）和分布容积（Vdss）降低了约65-70%。估计在有和没有脂质乳剂给药的情况下，血浆中CyA的游离分数分别为0.05 +/- 0.01和0.17 +/- 0.06。脂质乳剂与CyA联合给药降低了ClTOT和Vdss，导致快速消除，即CyA从体内的t1/2降低。
