Study On The Clinical Pharmacokinetics Of Metformin Hydrochloride Sustained Release Tablet

AIM: To study the clinical pharmacokinetics and the bioavailability of metformin hydrochloride sustained release tablet. METHOD: According to a 2-circle randomized crossover design, each of the 20 healthy men was administrated by a single, multi oral doses of metformin hydrochloride sustained tablet (test drug) and sailed metformin hydrochloride tablet (reference drug),respectively. The concentrations of metformin in plasma samples at different time points were determined by LC/MS/MS and the plasma concentrations-time profiles were obtained. We described the pharmacokinetic parameters and assessed the relative bioavailability, and explained the test drug had sustained characteristics.RESULTS: Following a single oral dose of metformin 500 mg (test drug) and 500mg (reference drug), the Cmax values were 736±264 and 1062±276 ng/ml, respectively. The Tmax values were 3.98±1.38 and 2.78±0.79h, respectively; the AUCO-t values were 5910±1767 and 6175±1597 ng·h/ml, respectively. The AUC0-( values were 6150±1889 and 6291±1604 ng·h/ml. The bioavailability was 100.6±35.2%. After administrating multi oral doses (test drug, once every day, 100 mg once)and reference drug (twice every day, 500 mg once) to get stable state, the Cmax values were 801±184 and 935±329 ng/ml,respectively. The Cmin values were 91.2±38.6 and 118.2±77.1 ng/ml. The Cav values were 400±70和429±90 ng/ml, respectively. The DF values were 1.79±0.46 and 1.91±0.60. The AUCss values were 9612±1681 and 10292±2152 ng h/ml. The bioavailabitity was 94.9±13.5%. CONCLUSION: Comparing test drug with reference drug, the values of Cmax and Tmax have obvious differences. The Cmax value of test drug was lower than reference drug, but the value of Tmax has much longer and the value of DF is smaller than reference drug.This showed test drug had obvious sustained release characteristics.