伊曲康唑Pluronic P123/RH40聚合物胶束在大鼠体内的药动学

Pharmacokinetics of Pluronic P123/RH40 polymeric micelles of itraconazole in rats

目的:研究伊曲康唑Pluronic P123/RH40(ITZ-P123/RH40)聚合物胶束在大鼠体内的药动学行为。方法:大鼠随机分为4组,每组6只,分别在禁食和正常饮食情况下灌胃给予ITZ-P123/RH40聚合物胶束和斯皮仁诺胶囊(Sporanox)。HPLC法测定大鼠体内血浆药物浓度,用DAS 2.0软件计算药动学参数。结果:ITZ-P123/RH40聚合物胶束组无论是否禁食,都可显著提高ITZ的AUC0-∞和Cmax(P<0.01),AUC0-∞和Cmax分别提高了162%和242%(禁食),110%和50%(正常饮食)。聚合物胶束组药物吸收基本不受饮食影响,无论是否禁食,主要药动学参数并无明显变化,但Sporanox组ITZ的吸收受饮食影响明显。结论:胶束给药系统也许可以作为一种新的口服给药系统,以提高伊曲康唑的口服生物利用度,同时减少食物对其吸收的影响。

Objective： To investigate the pharmacokinetics of Pluronic P123/RH40 （P123/RH40） poly- meric micelles of itraconazole in rats. Methods： Six rats were orally administered with P123/RH40 micelles or Sporanox capsules in fasted state or fed normal diet. HPLC was used to determine the drug concentration in rat plasma. The pharmacokinetic parameters were calculated using DAS 2.0 software program. Results ： After adminis- tration of the P123/RH40 micelles, AUC0-∞ and C were increased by 162% and 242% in the fasted state and by 110% and 50% in the fed state, respectively, as compared with those of the Sporanox capsules. Moreover, food had a marked effect on itraconazole absorption for Sporanox capsules, whereas the influence was less pronounced for P123/RH40 micelles. Conclusion： The new micelle formulation improves oral itraconazole bioavailability and re- duces food effect on its absorption, which may be an alternative oral formulation.