2种罗格列酮钠制剂在犬体内的生物等效性研究

Bioequivalence of 2 Kinds of Rosiglitazone Sodium Preparations in Dogs

目的:比较罗格列酮钠肠溶制剂与罗格列酮钠普通制剂在犬体内的药动学特征及其生物等效性。方法:将6只犬均分为2组,分别单次灌服罗格列酮钠肠溶胶囊或罗格列酮钠普通胶囊4mg,于给药前及给药后450min内后腿静脉取血,给药7d后,相同剂量自身交叉给药,于上述相同时间点取血,用高效液相色谱法测定血浆中罗格列酮浓度;经DAS2.0软件处理,计算药动学参数。结果:在相同剂量下,罗格列酮钠肠溶胶囊与其普通胶囊的药动学参数分别为AUC0～∞:(119.662±8.451)、(118.493±15.325)mg.min.L-1,t1/2Ka:(101.548±6.526)、(39.702±26.293)min,cmax:(0.359±0.035)、(0.807±0.208)mg.L-1;与普通胶囊比较,肠溶胶囊的AUC0～∞无显著性差异,t1/2Ka明显延长、cmax明显降低(P<0.05或P<0.01)。结论:与普通胶囊比较,罗格列酮钠肠溶制剂与其生物等效且具有明显的缓释特征。

OBJECTIVE： To compare pharmacokinetic characteristics and bioequivalence of Rosiglitazone sodium enteric-release capsule and Rosiglitazone sodium capsule in dogs. METHODS： 6 dogs were divided into two groups, Both groups were given Rosiglitazone sodium enteric-release capsule or Rosiglitazone sodium capsule 4 mg respectively in randomized cross-over study. Blood samples of hind legs vein were collected before administration and within 450 rain after administration. The plasma concentration of rosiglitazone was measured by HPLC. The pharmacokinetic parameters of rosiglitazone were calculated using DAS 2.0 software. RESULTS： The pharmacokinetic parameters of same dosage of Rosiglitazone sodium enteric-release capsules vs. Rosiglitazone sodium capsules were as follows： AUC0-∞： （119.662 ± 8.451） mg.min.L^-1 vs. （118.493 ± 15.325） mg.min. L^-1; t1/2Ka： （101.548 ± 6.526） min vs. （39.702±26.293） min; cmax： （0.359± 0.035） mg.L^-1 vs. （0.807 ± 0.208） mg.L^-1. Compared with normal capsule, AUC0-∞ of enteric-release capsule had no significant difference, t1/2Ka extended and cmax decreased significantly （P〈 0.05 or P〈0.01）. CONCLUSION： Rosiglitazone sodium enteric-release capsules and common capsule are bioequivalente and characterized with sustained-release profile.