A Combined Single Dose Study Under Fasting Condition And Multiple Doses Study Under Normal Diabetic Meal Comparing the Bioavailability of Two Formulations of 500 mg Metformin Hydrochloride Extended Release Tablets.

On Day 1, to obtain pharmacokinetic profile of a single dose, the test or reference drugs were given with 200 mL of water and swallowed without chewing the drug. For multiple doses administration at Day 2 until Day 5, the study drugs were administered at a regimen of one tablet each day, 30 minutes after breakfast. Time of drug administration was standardized for all participating subjects throughout the study period. From each subject, on Day 1 until Day 5 blood samples were drawn 5 mL before breakfast and drug administration; and breakfast was provided only on Day 2 until Day 5. Only on Day 1 and Day 5 after drug administration, the blood samples were drawn 5 mL each at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours. The blood samples drawn on Day 1 were used to show the single dose pharmacokinetic profile under fasting condition; while those drawn on Day 5 were used to show the multiple-dose-pharmacokinetic profile after meal intake. One week after the first drug administration (washout period), the same procedure was repeated with the alternate drug. The plasma concentrations of metformin were determined by high performance liquid chromatography with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed in the single dose study were AUCt, AUCinf, Cmax, tmax, and t1/2. The pharmacokinetic parameters assessed in multiple doses study at steady state phase were AUCtau, Cmax, Cmin, and t1/2.