Metformin OralMonograph - Metformin Hydrochloride
Class: BIGUANIDES(68:20.04)
Sections: Uses | Dosage and Administration | Cautions | Drug Interactions | Acute Toxicity | Pharmacology | Pharmacokinetics | Chemistry and Stability | Preparations
Dosage and Administration ?Administration Metformin is administered orally. In patients receiving a metformin hydrochloride conventional tablets at a dosage of 2 g or less daily, the drug usually can be given as 2 divided doses daily; however, in patients who require more than 2 g daily, the drug usually should be administered as 3 divided doses daily. Metformin hydrochloride in fixed combination with pioglitazone or rosiglitazone is administered in divided doses daily with meals to reduce the gastrointestinal effects of the metformin hydrochloride component.
Although food decreases the extent and slightly delays absorption of metformin conventional tablets, the manufacturer states that the clinical importance of these effects is not known and recommends that the drug be taken with meals to decrease adverse GI effects. PharmacokineticsThe pharmacokinetics of metformin in patients with normal renal function do not appear to be affected by gender, race, or the presence of diabetes mellitus. Following administration of a single 500-mg dose of metformin hydrochloride as conventional tablets with food in pediatric patients (12?16 years of age) with type 2 diabetes mellitus, mean peak plasma concentrations and area under the concentration-time curve (AUC) differed less than 5% compared with those values in healthy adults; all patients had normal renal function. In pediatric patients 11?16 years of age receiving a single dose of metformin in fixed combination with glyburide, mean dose-normalized glyburide peak plasma concentration and AUC differed less than 6% from historical values in healthy adults.
Bioequivalence has been demonstrated between the fixed combination of rosiglitazone and metformin and each agent given concurrently.
?Absorption Metformin is slowly and incompletely absorbed from the GI tract, mainly from the small intestine; absorption is complete within 6 hours. The absolute oral bioavailability of the drug under fasting conditions is reported to be approximately 50?60% with metformin hydrochloride doses of 0.5?1.5 g; binding of the drug to the intestinal wall may explain the difference between the amount of drug absorbed (as determined by the urinary and fecal excretion of unchanged drug) and the amount bioavailable in some studies. In single-dose studies with metformin hydrochloride conventional tablets doses of 0.5?1.5 g or 0.85?2.55 g, plasma metformin concentrations did not increase in proportion to increasing doses, suggesting an active saturable absorption process. Similarly, in single-dose studies with an extended-release tablet preparation (Glumetza?) at doses of 0.5?2.5 g, plasma metformin concentrations did not increase in proportion to increasing doses. At steady state after administration of a metformin hydrochloride extended-release tablet preparation (Glucophage? XR), the AUC and peak plasma concentrations were not dose proportional within the range of 0.5?2 g. However, limited data from studies in animals and in human intestinal cell cultures suggest that transepithelial transfer of metformin in the intestine may occur through a passive, nonsaturable mechanism, possibly involving a paracellular route. In several studies with another metformin hydrochloride extended-release tablet preparation (Fortamet?) using doses of 1?2.5 g, metformin exposure was dose-related.
Food decreases and slightly delays the absorption of metformin conventional tablets; the clinical importance of these effects is unknown. (See Dosage and Administration: Administration.) Administration of metformin hydrochloride conventional tablets with food reportedly has decreased peak plasma concentrations of the drug by 35?40%, reduced area under the plasma concentration-time curve (AUC) by 20?25%, and delayed time to peak plasma drug concentration by 35?40 minutes compared with these parameters in fasting individuals receiving this metformin preparation. However, in one study, concomitant administration of the drug as conventional tablets with food had a less pronounced effect (average reduction in bioavailability of 10%) on absorption.
Referencehttp://www.medscape.com/druginfo/monographcid=med&drugid=11285&drugname=Metformin+Oral&monotype=monograph&secid=8
