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  • 杜施霖,耿文叶,童朝阳.格列齐特缓释片在比格犬体内的药动学及生物等效性[J].第二军医大学学报,2019,40(10):1162-1166    [点击复制]
  • DU Shi-lin,GENG Wen-ye,TONG Chao-yang.Pharmacokinetics and bioequivalence of gliclazide modified release tablets in Beagle dogs[J].Acad J Sec Mil Med Univ,2019,40(10):1162-1166   [点击复制]
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格列齐特缓释片在比格犬体内的药动学及生物等效性
杜施霖1,耿文叶2,童朝阳1*
0
(1. 复旦大学附属中山医院急诊科, 上海 200032;
2. 复旦大学药学院药剂学教研室, 上海 201203
*通信作者)
摘要:
目的 研究自制格列齐特缓释片在比格犬体内的药动学行为和体内外相关性。方法 取6条比格犬随机分成两组,采用自身对照交叉方式给药,分别灌胃给予自制格列齐特缓释片和参比制剂达美康,给药剂量为30 mg。给药后于不同时间点采血,采用高效液相色谱法测定血药浓度,计算药动学参数,考察自制格列齐特缓释片的药动学特征和相对生物利用度,评价其生物等效性,计算其体内外相关性。结果 达美康的药时曲线下面积(AUC0-∞)为(101.74±20.29)μg/(mL·h),自制制剂格列齐特缓释片的AUC0-∞为(95.40±28.68)μg/(mL·h),两者间各药动学参数差异均无统计学意义(P>0.05)。自制格列齐特缓释片对达美康的相对生物利用度为93.77%,两者具有生物等效性。将制剂在犬体内的吸收分数与体外累积释药率作线性回归,达美康与自制格列齐特缓释片的相关系数分别为0.912和0.894,均大于临界值(r0.05,7=0.754),两者的体外释放速率与犬体内吸收速率均相关。结论 自制格列齐特缓释片在比格犬体内具有缓释特征,其与参比制剂达美康生物等效。本研究建立的体外释放度测定方法可用于预测格列齐特缓释片在体内的吸收行为。
关键词:  格列齐特  迟效制剂  比格犬  高效液相色谱法  药代动力学
DOI:10.16781/j.0258-879x.2019.10.1162
投稿时间:2019-07-09修订日期:2019-09-11
基金项目:上海市卫生和计划生育委员会重要薄弱学科建设项目(2016ZB0202).
Pharmacokinetics and bioequivalence of gliclazide modified release tablets in Beagle dogs
DU Shi-lin1,GENG Wen-ye2,TONG Chao-yang1*
(1. Department of Emergency, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
2. Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
*Corresponding author)
Abstract:
Objective To explore the pharmacokinetics of self-made gliclazide modified release tablets in Beagle dogs and to evaluate the in vivo and in vitro correlation. Methods Six Beagle dogs were orally given self-made gliclazide modified release tablets or reference preparation (DaMeiKang) at a dose of 30 mg with self-control cross-over method. Blood samples were collected at different time points after administration. The gliclazide concentration in plasma was determined by high-performance liquid chromatography, and the pharmacokinetic parameters were calculated. The pharmacokinetic characteristics and relative bioavailability of self-made gliclazide modified release tablets were investigated, the bioequivalence was evaluated, and the in vivo and in vitro correlation was calculated. Results Area under curve (AUC0-∞) of DaMeiKang was (101.74±20.29) μg/(mL·h), and AUC0-∞ of self-made gliclazide modified release tablets was (95.40±28.68) μg/(mL·h). There were no significant differences in the pharmacokinetic parameters between the test and reference formulations (P>0.05). The relative bioavailability of self-made gliclazide modified release tablets was 93.77%, which was bioequivalent with the reference preparation. The in vitro and in vivo correlation analysis showed that the correlation coefficients of DaMeiKang and self-made gliclazide modified release tablets were 0.912 and 0.894, respectively, which were higher than the critical value (r0.05, 7=0.754). The in vitro release rates of the two preparations were correlated with the in vivo absorption rates. Conclusion The self-made gliclazide modified release tablets have sustained-release characteristics and bioequivalence with reference preparation. The in vivo absorption behavior of gliclazide modified release tablets can be predicted by the in vitro release assay established in this study.
Key words:  gliclazide  delayed-action preparations  Beagle dogs  high-performance liquid chromatography  pharmacokinetics