Metformin Extended Release Tablets
Absorption and Bioavailability
Following a single oral dose of metformin hydrochloride extended release tablets USP, Cmax is achieved with a median value of 7 hours and a range of 4 hours to 8 hours.
Peak plasma levels are approximately 20% lower compared to the same dose of metformin hydrochloride tablets however, the extent of absorption (as measured by AUC) is similar to metformin hydrochloride tablets.
At steady state, the AUC and Cmax are less than dose proportional for metformin hydrochloride extended release tablets USP within the range of 500 mg to 2000 mg administered once daily. Peak plasma levels are approximately 0.6, 1.1, 1.4, and 1.8 μg/mL for 500, 1000, 1500, and 2000 mg once-daily doses, respectively. The extent of metformin absorption (as measured by AUC) from metformin hydrochloride extended release tablets USP at a 2000 mg once-daily dose is similar to the same total daily dose administered as metformin hydrochloride tablets 1000 mg twice daily. After repeated administration of metformin hydrochloride extended release tablets USP, metformin did not accumulate in plasma.
Within-subject variability in Cmax and AUC of metformin from metformin hydrochloride extended release tablets USP is comparable to that with metformin hydrochloride tablets.
Although the extent of metformin absorption (as measured by AUC) from the metformin hydrochloride extended release tablet USP increased by approximately 50% when given with food, there was no effect of food on Cmax and Tmax of metformin. Both high and low fat meals had the same effect on the pharmacokinetics of metformin hydrochloride extended release tablets USP.
Metformin Hydrochloride Pharmacokinetics
Approximately 50–60% (absolute) with dosages of 0.5–1.5 g.1 2 3 4 18 33 43 50 65 72 85 89
Fixed-combination preparation containing 500 mg of metformin hydrochloride and 4 mg of rosiglitazone is bioequivalent to mg-equivalent dosages of individual components administered separately under fasted conditions.247
Therapeutic response usually apparent within a few days to 1 week.18 53 72 98 134 Maximal glycemic response within 2 weeks.18 53 72 98 134
Blood glucose concentrations increase within 2 weeks following discontinuance of metformin therapy.53 134
Food decreases and slightly delays absorption of conventional tablets.1 2 3 4 18 208 314
Food increases the extent of absorption of extended-release tablets (Glucophage XR, Fortamet).1 258 Peak plasma concentrations and time to achieve peak plasma concentrations not altered by administration of one extended-release preparation (Glucophage XR) with food; 1 food increases peak plasma concentrations and prolongs time to peak plasma concentrations of another extended-release tablet preparation (Fortamet).258
Peak concentrations and AUC of the extended-release metformin hydrochloride component increased by approximately 98 and 85%, respectively, when Actoplus Met XR was given with food.260 Time to peak concentration prolonged by approximately 3 hours for pioglitazone and 2 hours for extended-release metformin hydrochloride under fed conditions.260
Food increases the extent of absorption and delays the time to peak plasma concentrations of the oral solution.257 Fat content of meals does not appreciably affect the pharmacokinetics of metformin hydrochloride oral solution.257
Rapidly distributed into peripheral body tissues and fluids, particularly GI tract.30 50 65 72 89 134 162 167
Slowly distributed into erythrocytes and a deep tissue compartment (probably GI tissue).30 50 65 72 89 134 162 167
Plasma Protein Binding
Negligible.1 18 50 51 65 85 89
Not metabolized in the liver or GI tract and not excreted into bile.1 50 51 89 No metabolites identified in humans.1 50 51 89 314
Excreted in urine (approximately 35–52%)50 51 89 and feces (20–33%).6 33 43 50 72 89 Eliminated as unchanged drug.1 2 6 33 50 63 65 75 85 89 314
Approximately 6.2 hours.
- Metformin Information for Consumers
- Metformin Information for Healthcare Professionals (includes dosage details)
- Side Effects of Metformin (detailed)
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