复方盐酸二甲双胍片在健康人体的药代动力学和相对生物利用度  

Pharmacokinetics and relative bioavailability of compound metformin hydrochloride tablet in healthy volunteers

作　　者：魏敏吉[1] 吕媛[1] 康子胜[1] 李曼宁[1] 张朴[1] 刘燕[1] 钟大放[2] 陈笑艳[2] 朱林[2] 张勇[2] 李小燕[2] 

机构地区：[1]北京大学临床药理研究所,北京100083 [2]沈阳药科大学药物代谢与药物动力学实验室,辽宁沈阳100016

出　　处：《中国临床药理学杂志》2005年第1期41-45,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究复方盐酸二甲双胍片在健康人体的药代动力学和相对生物利用度。方法用交叉给药方法,22名健康受试者单次口服盐酸二甲双胍片1000mg加格列本脲片5mg(参比制剂)或复方盐酸二甲双胍片(试验制剂:盐酸二甲双胍1000mg,格列本脲5mg)。用HPLC法测定血清中盐酸二甲双胍浓度,用LC-MS方法测定血清中格列本脲浓度。用3P97程序以房室模型计算药代动力学参数。结果主要药代动力学参数,试验与参比制剂中盐酸二甲双胍的达峰时间tmax分别为(2.36±0.69),(2.41±0.70)h;Cmax分别为(1.42±0.28),(1.36±0.28)mg·L-1;t1/2分别为(5.18±1.62),(6.25±1.42)h;AUC0-24分别为(10.22±1.53),(10.07±1.81)mg·h·L-1。试验制剂的相对生物利用度为(99.3±13.2)%。参比与试验制剂中格列本脲的达峰时间tmax分别为(2.70±0.60),(2.60±0.50)h;Cmax分别为(181.1±58.3),(214.3±8.01)ng·mL-1;t1/2分别为(6.79±1.96),(6.67±1.92)h;AUC0-24分别为(0.99±0.28),(1.14±0.42)mg·h·L-1。试验制剂的相对生物利用度为(113.2±23.9)%。结论参比与试验制剂具有生物等效性。Objective To study the pharmacokinetics and relative bioavai- lability of compound metformin hydrochloride tablets. Methods A single oral doses of 1 000 mg metformin hydrochloride(MET) plus 5mg glyburide(GLY) (reference) and MET/GLY(test) were given to 22 healthy volunteers in an open randomized crossover design. The concentrations of MET in serum were determined by a validated HPLC method, while the concentrations of GLY in serum were determined by a validated LC-MS method. The pharmacokinetic parameters were calculated by 3P97 software(compartment model). Results The main pharmacokinetic parameters of MET were as follow: t max were (2.36±0.69)and (2.41±0.70)h , C max were (1.42±0.28)and(1.36±0.28)g·L -1,t 1/2 were (5.18±1.62)and( 6.25±1.42)h, AUC 0-24 were (10.22±1.53)and (10.07±1.81) mg·h·L -1 for test and reference respectively.Pharmacokinetic parameters of GLY were as follow: t max were (2.70±0.60)and (2.60±0.50)h , C max were (181.1±58.3)and (214.3±8.01) ng·mL -1,t 1/2 were (6.79±1.96)and (6.67±1.92) h, AUC 0-24 were (0.99±0.28) and (1.14±0.42) mg·h·L -1.The relative bioavailability of MET were (99.3±13.2) %, and (113.2±23.9 )% for GLY. Conclusion The pra-perations test and reference were bioequivalent.

关 键 词：复方盐酸二甲双胍片 格列本脲 生物等效性 药代动力学 高效液 相色谱法 液相色谱-质谱法 

分 类 号：R969.1[医药卫生—药理学] R977.15[医药卫生—药学]