AIM: To investigate the relative bioavailability of the test complex Metformin hydrochloride formulations (1.25 mg glibenclaminde and 250 mg metformin hydrochloride per pellet) and evaluate its bioequivalence of the c...AIM: To investigate the relative bioavailability of the test complex Metformin hydrochloride formulations (1.25 mg glibenclaminde and 250 mg metformin hydrochloride per pellet) and evaluate its bioequivalence of the complex compared with individual drug adminstration. METHODS: A randomized, self-control, two-way crossover studies were conducted in 20 healthy volunteers[(24±4) years, (62±7) kg, weight index (21.0±1.9)]. One pellet of fest drug or two pellets of reference (commercially available, 1.25 mg glibenclaminde per pellet and 250 mg Metformin hydrochloride per pellet respectively) were orally administrated and the alternative ones were administrated after a washout time of one week. Serum samples were collected before and after administration within 24 hours. Metformin and glibenclaminde concentrations in serum were measured by HPLC. Pharmacokinetic parameters were analyzed by 3P97 computer program. Cmax, tmax were calculated by raw data, AUC(0-last) was also calculated by the trapezoidal summation method. T-test was applied for the all pharmacokinetic parameters of the test and reference drug, the bioequivalence of Cmax, tmax and AUC(0-last) was analyzed by DAS 1.0 computer program package. RESULTS: The tmax, Cmax, t1/2Ka, t1/2Ke of glibenclaminde were as follows(test vs reference): (2.9±0.6) vs (2.8±0.6) h, (112±26) vs (117±28) μg/L, (1.6±0.4) vs (1.5±0.5) h, (1.6±0.4) vs (1.5±0.5) h, and AUC(0-last), AUC0-∝ were (607±109) vs (608±124) μg·L-1·h, (663±124) vs (655±127) mg·L-1·h, respectively. All parameters of mertiform were: tmax (2.0±0.8) vs (2.0±1.2) h, Cmax (1.7±0.4) vs (1.7±0.5) μg/L, t1/2Ka (0.5±0.5) vs (0.6±0.5) h, t1/2Ke (3.2±1.5) vs (2.8±0.9) h, respectively, and AUC(0-last) (8.4±2.4) vs (8.8±2.6), AUC0-∝ (8.9±2.4) vs (9.3±2.7) mg·L-1·h, respectively. There was no significant difference of all parameters between the test drug and the reference (P>0.05) which indicated the pharmacokinetic property of these two were similar. The relative bioavailability of glibenclaminde and mertiform in test drug were 101%±14% and 106%±22%. The analysis of variance tests on Cmax, tmax and AUC(0-last) of glyburide and Metformin right after conversion were qualified. The mean square analysis and two-side t-test of log-transformed data of the Cmax, tmax and AUC(0-last) of glibenclaminde and mertiformare were also qualified. CONCLUSION: The glibenclaminde and mertiform in the test complex pellet are bioequivalent of that of the reference.展开更多
文摘AIM: To investigate the relative bioavailability of the test complex Metformin hydrochloride formulations (1.25 mg glibenclaminde and 250 mg metformin hydrochloride per pellet) and evaluate its bioequivalence of the complex compared with individual drug adminstration. METHODS: A randomized, self-control, two-way crossover studies were conducted in 20 healthy volunteers[(24±4) years, (62±7) kg, weight index (21.0±1.9)]. One pellet of fest drug or two pellets of reference (commercially available, 1.25 mg glibenclaminde per pellet and 250 mg Metformin hydrochloride per pellet respectively) were orally administrated and the alternative ones were administrated after a washout time of one week. Serum samples were collected before and after administration within 24 hours. Metformin and glibenclaminde concentrations in serum were measured by HPLC. Pharmacokinetic parameters were analyzed by 3P97 computer program. Cmax, tmax were calculated by raw data, AUC(0-last) was also calculated by the trapezoidal summation method. T-test was applied for the all pharmacokinetic parameters of the test and reference drug, the bioequivalence of Cmax, tmax and AUC(0-last) was analyzed by DAS 1.0 computer program package. RESULTS: The tmax, Cmax, t1/2Ka, t1/2Ke of glibenclaminde were as follows(test vs reference): (2.9±0.6) vs (2.8±0.6) h, (112±26) vs (117±28) μg/L, (1.6±0.4) vs (1.5±0.5) h, (1.6±0.4) vs (1.5±0.5) h, and AUC(0-last), AUC0-∝ were (607±109) vs (608±124) μg·L-1·h, (663±124) vs (655±127) mg·L-1·h, respectively. All parameters of mertiform were: tmax (2.0±0.8) vs (2.0±1.2) h, Cmax (1.7±0.4) vs (1.7±0.5) μg/L, t1/2Ka (0.5±0.5) vs (0.6±0.5) h, t1/2Ke (3.2±1.5) vs (2.8±0.9) h, respectively, and AUC(0-last) (8.4±2.4) vs (8.8±2.6), AUC0-∝ (8.9±2.4) vs (9.3±2.7) mg·L-1·h, respectively. There was no significant difference of all parameters between the test drug and the reference (P>0.05) which indicated the pharmacokinetic property of these two were similar. The relative bioavailability of glibenclaminde and mertiform in test drug were 101%±14% and 106%±22%. The analysis of variance tests on Cmax, tmax and AUC(0-last) of glyburide and Metformin right after conversion were qualified. The mean square analysis and two-side t-test of log-transformed data of the Cmax, tmax and AUC(0-last) of glibenclaminde and mertiformare were also qualified. CONCLUSION: The glibenclaminde and mertiform in the test complex pellet are bioequivalent of that of the reference.
