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Introduction of
Galanthamine HBr
Galantamine (trade
names Razadyne, Razadyne ER, Reminyl, Nivalin) is a drug
developed by Janssen Pharmaceutica, and used for the treatment
of mild to moderate Alzheimer’s disease. It is an alkaloid
that is obtained from the bulbs and flowers of Caucasian
snowdrop (Voronov’snowdrop), Galanthus woronowii (Amaryllidaceae)
and related species. The active ingredient was discovered
accidentally by a Bulgarian pharmacologist in the 1950s.
Pharmacology
of Galanthamine HBr
Galantamine in its pure form is a white powder. Galantamine is
a competitive and reversible cholinesterase inhibitor. It is
believed it works by enhancing cholinergic function by
increasing the concentration of acetylcholine in the brain.
The atomics resolution 3D structure of the complex of
galantamine and its target, acetylcholinesterase, was
recentely determined by X-ray crystallography. There is no
evidence that galantamine alters the course of the underlying
dementing process. Galantamine has also shown activity in
modulating the nicotinic cholinergic receptors to increase
acetylcholine release.
Pharmacokinetics of Galanthamine HBr
Absorption of galantamine is rapid and complete and shows
linear pharmacokinetics. It is well absorbed with absolute
oral bioavailability between 80 and 100%. It has a half-life
of 7 hours. Peak effect of inhibiting acetylcholinesterase was
achieved about one hour after a single oral dose of 8 mg in
healthy volunteers.
Plasma protein binding of galantamine is about 18%, which is
relatively low.
Metabolism of Galanthamine HBr
The major route of metabolism for galantamine is through the
liver, this accounts for approximately 75% of the total
metabolism of galantamine. Hepatic cytochrome P450 (CYP)
isoenzymes are the active enzymes for this metabolic route. In
vitro studies have shown that CYP2D6 and CYP3A4 are involved
in galantamine metabolism.
For Razadyne ER (the once-a-day formulation), CYP2D6 poor
metabolizers had drug exposures that were approximately 50%
higher than for extensive metabolizers. About 7% of the
population has this genetic mutation, however because the drug
is individually titrated to tolerability, no specific dosage
adjustment is necessary for this population.
Indications of Galanthamine HBr
Galantamine is indicated for mild to moderate dementia of the
Alzheimer’s type. It has been studied in Mild Cognitive
Impairment (MCI) without demonstrating a statistically
significant effect.
The U.S. Food and Drug Administration (FDA) sent out a warning
indicating that the product should not be used in MCI patients
because of increased mortality observed in trials for MCI with
galantamine.
Available forms of Galanthamine HBr
The product is supplied in twice-a-day tablets, once-a-day
extended release capsules, and in oral solution. The tablets
come in 4mg, 8mg and 12 mg forms. The capsules come in 8mg,
16mg, and 24mg forms.
Adverse events of Galanthamine HBr
In clinical trials, galantamine’s side effect profile was very
similar to that of other cholinesterase inhibitors, with
gastrointestinal symptoms being the most notable and most
commonly observed. In practice, some other cholinesterase
inhibitors might be better tolerated, however a careful and
gradual titration over more than three months may lead to
equivalent long-term tolerability.
Disclaimer:
Information on this page is provided for general
information purposes. You should not make a clinical treatment
decision based on information contained in this page without
consulting other references including the package insert of
the drug, textbooks and where relevant, expert opinion. We
cannot be held responsible for any errors you make in
administering drugs mentioned on this page, nor for use of any
erroneous information contained on this page.
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