CLINICAL PHARMACOLOGY

Mechanism of Action

Brimonidine tartrate is an alpha adrenergic receptor agonist. It has a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.

Pharmacokinetics

After ocular administration of a 0.2% solution, plasma concentrations peaked within 1 to 4 hours and declined with a systemic half-life of approximately 3 hours.

In humans, systemic metabolism of brimonidine tartrate is extensive. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites. Approximately 87% of an orally-administered radioactive dose was eliminated with 120 hours, with 74% found in the urine.

CLINICAL STUDIES

Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Brimonidine tartrate has the action of lowering intraocular pressure with minimal effect on cardiovascular and pulmonary parameters.

In comparative clinical studies with timolol 0.5%, lasting up to one year, the IOP lowering effect of brimonidine tartrate 0.2% was approximately 4-6 mm Hg compared with approximately 6 mm Hg for timolol. In these studies, both patient groups were dosed twice daily, however, due to the duration of action of brimonidine tartrate, it is recommended that brimonidine tartrate be dosed three times daily. Eight percent of subjects were discontinued from studies due to inadequately controlled intraocular pressure, which in 30% of these patients occurred during the first month of therapy. Approximately 20% were discontinued due to adverse experiences.