Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Aurogen South Africa (Pty) Ltd, Woodhill Office Park, Building 1, 53 Phillip Engelbrecht Avenue, Meyersdal, Ext. 12, 1448, Johannesburg, South Africa
A 21.2 Oral-Hypoglycaemic
Metformin is a biguanide oral anti-hyperglycaemic agent. Its mode of action is thought to be due to increased peripheral glucose utilisation mediated by increased insulin sensitivity and inhibition of increased hepatic and renal gluconeogenesis.
After an oral dose of metformin, Tmax is reached in 2,5 hours. Absolute bioavailability of a 500 mg or 850 mg metformin tablet is approximately 50-60% in healthy subjects. After an oral dose, the non-absorbed fraction recovered in faeces is 20-30%.
After oral administration, metformin absorption is saturable and incomplete. It is assumed that the pharmacokinetics of metformin absorption is non-linear.
Steady state plasma concentrations are reached within 24 to 48 hours.
Food decreases the extent and slightly delays the absorption of metformin; following administration of a dose of 850 mg, a 40% lower plasma peak concentration, a 25% decrease in AUC (area under the curve) and a 35 minute prolongation of time to peak plasma concentrations were observed. The clinical relevance of these decreases is unknown.
Plasma protein binding is negligible. Metformin partitions into erythrocytes. The blood peak concentration is lower than the plasma peak concentration and appears at approximately the same time. The red blood cells most likely represent a secondary compartment of distribution. The mean Volume of Distribution ranges between 63-276 l.
Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.
Renal clearance of metformin is >400 mI/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6,5 hours.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.
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