Pharmacology

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. 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

Absorption of Galantamine is rapid and complete and shows linear pharmacokinetics. It is well absorbed with absolute oral bioavailability between 80-100%. 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

The major route of metabolism for Galantamine is through the liver, this about 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.

Clinical use

Indications

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 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 galanatamine.

Available Forms

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

In clinical trials, galantamine’s side effect profile is 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.

Source: wikipedia GFDL

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Page last modified: May 2007