摘要
目的:研究盐酸二甲双胍肠溶微丸胶囊的人体相对生物利用度和生物等效性。方法:健康志愿者20名,采用两周期交叉单剂量口服盐酸二甲双胍肠溶试验和参比制剂,于给药前和给药后16h内多点抽取肘静脉血,用高效液相色谱(HPLC)法测定血浆中盐酸二甲双胍的浓度,用DAS药动学程序计算相对生物利用度并评价两种制剂的生物等效性。AUC0-24和Cmax经方差分析和双单侧t检验,tmax进行秩和检验,(1-2α)置信区间分析。结果:单剂量口服二甲双胍肠溶试验制剂和参比制剂的Cmax分别为(46.3±21.1)μg·L-1和(44.6±17.4)μg·L-1;tmax分别为(1.1±0.5)h和(1.19±0.34)h;AUC0-24分别为(164.4±83.3)μg·L-1·h和(156.1±69.7)μg·L-1·h;AUC0-∞分别为(173.8±87.4)μg·L-1·h和(161.0±69.7)μg·L-1·h。Cmax,AUC(0-24)的90%可信区间分别为89.9%～112.1%,95.8%～109.8%。结论:试验制剂与参比制剂比较,其人体相对生物利用度为(104.1±18.5)%,两制剂具有生物等效性。
ABSTRACT：OBJECTIVE To study the relative bioavailability and bioequivalence of metfornain enteric-coated pellet coated capsules in Chinese healthy volunteers. METHODS A single oral dose （250 nag of tested and reference formulation） was given to 20 healthy volunteers in a randomized crossover study, with one week dose interval. The plasma naetformin concentrations was determined within 16 h administration by HPLC. The pharnaaeokinetie parameters were calculated and the bioavailability and hioequivalenee of two formulations were evaluated by DAS program. AUC0-24 and C was analyzed by ANOVA followed by test,tmax was analysed by rank sum test. RESULTS After a single dose administration, the pharnaacokinetic parameters for metformin enteric-coated pellet capsules were as follows：Cmax was （46. 3 ±21.1）μg·L^-1 and （44. 6 ± 17.4）μg·L^-1 ,tmax was （1.13±0.5） h and （1.19±0.34） h; AUC0-24 was （164.4±83.3） μg·L^-1·h and （156. 1 ±69. 7）μg·L^-1·h AUG0-24 was （173.8± 87. 4） μg·L^-1·h and （161.0± 69. 7） μg·L^-1·h for T and R respectively. The 90% confidential interval of C AUC（0-24） of tested formulation was 89. 9% - 112. 1 % and 95.8% - 109.8%, respectively. CONCLUSION The relative bio availability of the tested for mulations compared with the reference formulations was （104. 1 ± 18.5） %. The statistic analysis shows that the two formulations were bioequivalence.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2010年第19期1638-1641,共4页
Chinese Journal of Hospital Pharmacy
