Pharmacokinetics
The gastrointestinal tract quickly absorbs metformin, and the maximum plasma concentrations happen 1-2 hours after oral administration. Although there is a significant amount of interindividual variability in the rate of absorption, the extent of absorption (AUC) increases proportionally to the dose administered.
Food does not reduce bioavailability. Metformin does not undergo hepatic metabolism (no cytochrome P450 involvement) and is excreted unchanged in the urine. Metformin renal clearance (CLr) is inversely correlated with creatinine clearance (CLcr). As renal function declines, CLcr declines and the half-life of metformin lengthens. There are no variations in the pharmacokinetics of single- and multiple-dose administration in patients with normal renal function.
Particular Populations
Elderly: There are no differences in the pharmacokinetics of single- and multiple-dose administration in elderly subjects with normal renal function.
Renal Impairment: In proportion to the severity of renal impairment, metformin's half-life is prolonged and its AUC is raised. less than 60 mL per minute of creatinine clearance). Patients with mild to moderate renal impairment (CLcr= 60-90 mL/min) don't need their dosage adjusted. When undergoing or just before an imaging procedure that uses iodinated contrast materials, metformin should be stopped because doing so may cause an abrupt change in renal function. Metformin serum concentrations are unaffected by dialysis.
Hepatic Impairment: In patients with hepatic impairment, the pharmacokinetics of metformin are unaffected. Patients with mild to moderate hepatic impairment do not need a dosage adjustment.
In patients with severe liver disease, metformin should be used with caution because higher serum concentrations of the drug may increase the risk of lactic acidosis. When undergoing or just before an imaging procedure that uses iodinated contrast materials, metformin should be stopped because doing so may cause an abrupt change in renal function.