环孢素A-Eudragit S100纳米粒冻干粉制剂在犬体内的药动学

Pharmacokinetic profile of freeze-dried cyclosporine A-Eudragit S100 nanoparticle formulation in dogs

目的:研究环孢素A-Eudragit S100纳米粒冻干粉制剂(freeze-dried cyclosporine A-Eudragit S100 nanoparticles,CyA-S100-NP)在家犬体内药动学及相对生物利用度。方法:以双周期交叉随机试验设计法,高效液相色谱法测定6只家犬口服给予环孢素A-Eudragit S100纳米粒冻干粉硬胶囊和新山地明微乳软胶囊(Neoral)后环孢素A的血药浓度,采用3P97软件计算药动学参数。结果:经3P97软件拟合,环孢素A的药动学过程符合二室模型。与Neoral相比,CyA-S100-NP的AUC显著增大(P<0.05),CL显著降低(P<0.05),相对生物利用度为135.9%。结论:CyA-S100-NP可促进药物口服吸收,显著提高环孢素A的生物利用度,有望开发成为一种新型口服环孢素A纳米粒固体制剂。

Objective： To study the pharmaceutical characteristics of freeze-dried cyclosporine A-Eudragit S100 nanoparticles（CyA-S100-NP）in dogs.Methods： A random and two-way crossover study was adopted in 6 dogs.The blood concentration was determined by internal standard HPLC method after oral administration of CyA-S100-NP and Neoral.Pharmacokinetics parameters were calculated using 3P97 program.Results： The concentration-time data were fitted as a two-compartment open model.The AUC of CyA-S100-NP was higher than that of Neoral（P0.05）,while the CL significantly decreased（P0.05）.The relative bioavailability of CyA-S100-NP was 135.9% as compared with Neoral.Conclusion： The bioavailability of CyA in CyA-S100-NP is significantly improved.CyA-S100-NP has the potential to develop a new CyA nanoparticle solid formulation.