LADMER SYSTEM OF LIBERATION

METFORMIN
L
Metformin is orally administered in the dose range of 500 mg/b.i.d. It is available in various
oral formulations such as Immediate tablets (IR) and Extended release (ER) tablets. In IR, this
process starts when the tablet is ingested then will be dissolved in the stomach because of
its acid which breaks diwn the tablet snd releases Metformin into the gastric fluids, now that
the drug will be absorb primarily from the upper part of the small intestine into the
bloodstream. In the ER, the same process happens but the release and absorption rate is
much slower.
ABSORPTION
Metformin is rapidly absorbed from the upper part of the

A
gastrointestinal tract (mainly the small intestine) after oral
administration. Its absorption is not affected by food intake. It has
an oral bioavailability of 40-60% and GI absorption is apparently
complete within 6 hrs of ingestion. Its hydrophilicity is associated DISTRIBUTION
with thelow intestinal and cell membran permeabilit, which is the
primary limiting step for its oral absorption. Metformin is distributed throughout the body, primarily in the plasma and
red blood cells. It does not significantly bind to plasma proteins. The drug
does not penetrate well into most tissues and is not known to cross the
blood-brain barrier. The volume of distribution has been reported to range

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from 63 to 276 L after intravenous administration. The concentration of
metformin in the liver is three to five fold higher than that in the portal vein
(40–70 μmol/L) after single therapeutic dose. As the antihyperglycemic
effect of metformin is mainly due to the inhibition of hepatic glucose
output and the concentration of metformin in the hepatocytes is much
higher than in the blood, the liver is therefore presumed to be the primary
site of metformin function.
METABOLISM
Metformin is not metabolized by the liver, and it is excreted unchanged in

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the urine. It remains in its active form throughout its journey in the body
and this is one of its unique characteristics, as many other drugs undergo
extensive hepatic metabolism. Metformin is relatively stable compound in
tge body, it is not prone to chemical breakdown or metabolism by the liver’s
enzymes. It’s stability allows it to be directly excreted from the body.

EXCRETION

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Metformin is primarily eliminated by the kidneys. The renal
clearance of Metformin exceeds the glomerular filtration rate,
indicating that it is actively secreted into the renal tubules. Its
elimination half-life is approximately 2-6 hours in individuals with
normal kidney function.
RESPONSE
The primary pharmacodynamic effect of Metformin is to

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lower blood glucose levels. It does this by reducing
hepatic glucose production (gluconeogenesis) and
increasing insulin sensitivity in peripheral tissues, such as
muscle cells. This results in improved glucose uptake by
cells and decreased glucose release from the liver.
Samonte, Esther P.
BSPH 2Y1-1