DESCRIPTION
Galantamine hydrobromide is a reversible, competitive acetylcholinesterase inhibitor. Galantamine hydrobromide is known chemically as (4aS,6R,8aS)-4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol hydrobromide. It has an molecular formula of C17H21NO3•HBr and a molecular weight of 368.27. Galantamine hydrobromide is a white to almost white powder and is sparingly soluble in water. The structural formula for galantamine hydrobromide is:
Galantamine hydrobromide extended-release capsule is available in opaque hard gelatin extended-release capsules of 8 mg (white), 16 mg (pink), and 24 mg (caramel) containing galantamine hydrobromide, USP equivalent to respectively 8, 16 and 24 mg galantamine base. Inactive ingredients include pregelatinised starch, hypromellose, hydroxy propyl cellulose, colloidal silicon dioxide, magnesium stearate. The 16 mg capsule also contains ferric oxide (red). The 24 mg capsule also contains FD & C Yellow 6 Lake (15 to 18%). The capsule shells contain gelatin, and sodium lauryl sulfate. The capsule shells also contain one or more of the following: titanium dioxide, iron oxide red, iron oxide yellow.
Imprinting ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, potassium hydroxide, and purified water.
CLINICAL PHARMACOLOGY
Mechanism of Action
Although the etiology of cognitive impairment in Alzheimer's disease (AD) is not fully understood, it has been reported that acetylcholine-producing neurons degenerate in the brains of patients with Alzheimer’s disease. The degree of this cholinergic loss has been correlated with degree of cognitive impairment and density of amyloid plaques (a neuropathological hallmark of Alzheimer’s disease).
Galantamine, a tertiary alkaloid, is a competitive and reversible inhibitor of acetylcholinesterase. While the precise mechanism of galantamine’s action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this mechanism is correct, galantamine’s effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that galantamine alters the course of the underlying dementing process.
Pharmacokinetics
Galantamine is well absorbed with absolute oral bioavailability of about 90%. It has a terminal elimination half-life of about 7 hours and pharmacokinetics are linear over the range of 8 to 32 mg/day.
The maximum inhibition of acetylcholinesterase activity of about 40% was achieved about one hour after a single oral dose of 8 mg galantamine in healthy male subjects.
Absorption and Distribution
Galantamine is rapidly and completely absorbed with time to peak concentration about 1 hour. Food did not affect the AUC of galantamine but Cmax decreased by 25% and Tmax was delayed by 1.5 hours. The mean volume of distribution of galantamine is 175 L.
The plasma protein binding of galantamine is 18% at therapeutically relevant concentrations. In whole blood, galantamine is mainly distributed to blood cells (52.7%). The blood to plasma concentration ratio of galantamine is 1.2.
Metabolism and Elimination
Galanta