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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 bioavailability of compound metformin hydrochloride tablets in healthy volunteers. Methods A total of 22 healthy volunteers received a single oral dose of metformin hydrochloride 1000 mg plus glyburide 5 mg (reference formulation) or metformin hydrochloride (single dose of test compound: metformin hydrochloride 1000 mg, glyburide 5 mg ). The concentration of metformin hydrochloride in serum was determined by HPLC method and the concentration of glyburide in serum was determined by LC-MS method. Pharmacokinetic parameters were calculated in a compartment model using the 3P97 program. Results The main pharmacokinetic parameters, the peak tmax of metformin hydrochloride in test and reference preparations were (2.36 ± 0.69) and (2.41 ± 0.70) h, respectively, and the values of Cmax were (1.42 ± 0.28) and (1.36 ± 0.28) mg · L-1; t1 / 2 were (5.18 ± 1.62) and (6.25 ± 1.42) h respectively; AUC0-24 were (10.22 ± 1.53) and (10.07 ± 1.81) mg · h · L-1, respectively. The relative bioavailability of the test formulation was (99.3 ± 13.2)%. The peak tmax of glyburide in reference and test preparations were (2.70 ± 0.60) and (2.60 ± 0.50) h, respectively; the Cmax values were (181.1 ± 58.3) and (214.3 ± 8.01) ng · mL- t1 / 2 were (6.79 ± 1.96) and (6.67 ± 1.92) h respectively; AUC0-24 was (0.99 ± 0.28) and (1.14 ± 0.42) mg · h · L-1, respectively. The relative bioavailability of the test preparation was (113.2 ± 23.9)%. Conclusions Reference and test formulations are bioequivalent.