利用生物粘附技术提高萘哌地尔的生物利用度

IMPROVING BIOAVAILABILITY OF NAFTOPIDIL BY USING BIOADHESION IN DOGS

目的 为提高萘哌地尔生物利用度 ,制备生物粘附性萘哌地尔胶囊。方法 制备萘哌地尔胶囊、生物粘附胶囊I和II;比较两种生物粘附性胶囊与大鼠离体胃肠组织的粘附力 ;用自身对照方式单剂量分别给予家犬 3种胶囊 2 0 0mg ,比较 3种胶囊在家犬体内的药物动力学与生物利用度。结果 与普通胶囊相比 ,生物粘附性萘哌地尔胶囊I和II在家犬体内的血药峰浓度 (Cmax)下降 ,达峰时间 (Tmax)延迟 ,药时曲线下面积 (AUC0→∞)明显增加 ,两者为生物不等效制剂 ,与普通胶囊相比 ,萘哌地尔粘附胶囊I与II的生物利用度分别为 15 0 %± 14%和 15 4%± 2 3% ,两种生物粘附胶囊的药动学参数间无明显差异。

AIM To prepare naftopidil bioadhesive sustained release capsule and study their pharmacokinetics and relative bioavailability in the dog. METHODS Bioadhesive polymers such as hydroxypropyl methylcellulse (HPMC) and Carbopol 934 (CP 934) were used in capsule prescriptions. Naftopidil capsule and two formulations of bioadhesive sustained release capsules (I and II) were given to five healthy male dogs in a cross over test. The naftopidil concentrations in plasma were determined by a newly developed HPLC method and the pharmacokinetic parameters as well as the relative bioavailability were measured. RESULTS The C 0→∞ , C max and T max of naftopidil capsule was (3728±573) h·ng·mL -1 , (697±94) ng·mL -1 and (1 2±0 5) h. These parameters of bioadhesive sustained release capsule I and II, respectively, were (5518±391) h·ng·mL -1 and (5636±427) h·ng·mL -1 ; (468±61) ng·mL -1 and (512±72) ng·mL -1 ; both (4 0±0 7) h. Results from statistics showed that there were significant difference between bioadhesive formulations and the non bioadhesive one in C 0→∞ , C max and T max . The bioadhesive formulations and the non bioadhesive one were not bioequivalent, the relative bioavailability of the two bioadhesive sustained release capsules were respectively 150%±14% and 154%±23% when compared with the non bioadhesive capsule. CONCLUSION It is much improving bioavailability of naftopidil by using bioadhesion.