盐酸二甲双胍缓释片在中国健康受试者中的生物等效性研究
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摘要
目的评价2种盐酸二甲双胍缓释片(渗透泵型)在中国健康受试者的生物等效性。方法用开放、随机、单剂量、两制剂、两序列、两周期、交叉设计,空腹条件入组32例、餐后条件入组24例受试者;分别随机分为2组,单次口服试验药物和参比药物1000 mg,用液相色谱-串联质谱(LC-MS/MS)法测定血浆中二甲双胍的浓度,用Win Nonlin7. 0软件计算药代动力学参数,评价生物等效性。结果受试者服用受试制剂和参比制剂后,药代动力学参数如下:空腹组Cmax分别为(1. 21±0. 46),(1. 16±0. 39) mg·L~(-1); AUC0-t分别为(8. 85±2. 64),(8. 89±2. 48) mg·L~(-1)·h; AUC0-∞分别为(9. 03±2. 63),(9. 08±2. 49) mg·L~(-1)·h;餐后组Cmax分别为(1. 27±0. 22),(1. 24±0. 20)mg·L~(-1); AUC0-t分别为(11. 51±1. 84),(11. 22±2. 16) mg·L~(-1)·h; AUC0-∞分别为(11. 70±1. 88),(11. 35±2. 16) mg·L~(-1)·h。2种制剂的Cmax、AUC0-t和AUC0-∞经对数转换后90%可信区间分别为空腹状态下92. 06%～114. 40%,89. 22%～107. 42%和89. 19%～107. 29%;餐后状态下97. 11%～108. 36%,98. 07%～108. 94%和98. 32%～109. 48%。结论 2种盐酸二甲双胍缓释片(渗透泵型)在中国健康受试者体内具有生物等效性。
Objective To evaluate the bioequivalence of two kinds of metformin hydrochloride sustained-release tablets( osmotic pump type)in healthy Chinese subjects. Methods This was a single dose,open,random,two preparations,two sequences,two cycles,and cross design.A total of 32 subjects were enrolled under fasting condition and 24 subjects under fed condition. Subjects were randomly divided into two groups,single oral test drug and reference drug 1000 mg. The plasma concentration of metformin was determined by LC-MS/MS,and calculated by WinNonlin7. 0 software,to evaluate the bioequivalence. Results The main pharmacokinetic parameters of the test and reference preparations were as follows: the fasting state Cmaxwere( 1. 21 ± 0. 46),( 1. 16 ± 0. 39) mg·L~(-1); AUC0-twere( 8. 85 ± 2. 64),( 8. 89 ± 2. 48)mg·L~(-1)·h; AUC0-∞were( 9. 03 ± 2. 63),( 9. 08 ± 2. 49)mg·L~(-1)·h; the fed state Cmaxwere( 1. 27 ± 0. 22),( 1. 24 ± 0. 20)mg·L~(-1); AUC0-twere( 11. 51 ± 1. 84),( 11. 22 ± 2. 16) mg·L~(-1)·h;AUC0-∞were( 11. 70 ± 1. 88),( 11. 35 ± 2. 16) mg·L~(-1)·h. The 90%confidential interval of Cmax、AUC0-tand AUC0-∞of tested formulation in the fasting state were 92. 06%-114. 40%,89. 22%-107. 42% and 89. 19%-107. 29%; the fed state were 97. 11%-108. 36%,98. 07%-108. 94% and98. 32%-109. 48%. Conclusion Two kinds of metformin hydrochloride sustained-release tablets( osmotic pump type)were bioequivalent.
Objective To evaluate the bioequivalence of two kinds of metformin hydrochloride sustained-release tablets( osmotic pump type)in healthy Chinese subjects. Methods This was a single dose,open,random,two preparations,two sequences,two cycles,and cross design.A total of 32 subjects were enrolled under fasting condition and 24 subjects under fed condition. Subjects were randomly divided into two groups,single oral test drug and reference drug 1000 mg. The plasma concentration of metformin was determined by LC-MS/MS,and calculated by WinNonlin7. 0 software,to evaluate the bioequivalence. Results The main pharmacokinetic parameters of the test and reference preparations were as follows: the fasting state Cmaxwere( 1. 21 ± 0. 46),( 1. 16 ± 0. 39) mg·L~(-1); AUC0-twere( 8. 85 ± 2. 64),( 8. 89 ± 2. 48)mg·L~(-1)·h; AUC0-∞were( 9. 03 ± 2. 63),( 9. 08 ± 2. 49)mg·L~(-1)·h; the fed state Cmaxwere( 1. 27 ± 0. 22),( 1. 24 ± 0. 20)mg·L~(-1); AUC0-twere( 11. 51 ± 1. 84),( 11. 22 ± 2. 16) mg·L~(-1)·h;AUC0-∞were( 11. 70 ± 1. 88),( 11. 35 ± 2. 16) mg·L~(-1)·h. The 90%confidential interval of Cmax、AUC0-tand AUC0-∞of tested formulation in the fasting state were 92. 06%-114. 40%,89. 22%-107. 42% and 89. 19%-107. 29%; the fed state were 97. 11%-108. 36%,98. 07%-108. 94% and98. 32%-109. 48%. Conclusion Two kinds of metformin hydrochloride sustained-release tablets( osmotic pump type)were bioequivalent.
引文
[1]赵琳,梅勇,杨莉,等.渗透泵控释型盐酸二甲双胍缓释片Ⅱ(都乐宁)对2型糖尿病患者血糖水平控制的临床观察[J].中国医药指南,2014,12(29):135-136.
[2]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版)[J].中国实用内科杂志,2018,38(4):292-344.
[3]JABBOUR S,ZIRING B. Advantages of extended-release metformin in patients with type 2 diabetes mellitus[J]. Postgrad Med,2011,123(1):15-23.
[2]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版)[J].中国实用内科杂志,2018,38(4):292-344.
[3]JABBOUR S,ZIRING B. Advantages of extended-release metformin in patients with type 2 diabetes mellitus[J]. Postgrad Med,2011,123(1):15-23.