Alphagan/Alphagan P 0.1% Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: ALPHAGAN/ALPHAGAN P 0.1% is a relatively selective alpha-2 adrenergic 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: In humans, systemic metabolism of brimonidine 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 within 120 hours, with 74% found in the urine.
Alphagan: 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.
Alphagan P 0.1%: After ocular administration of either a 0.1% or 0.2% solution, plasma concentrations peaked within 0.5 to 2.5 hours and declined with a systemic half-life of approximately 2 hours.
Clinical studies/evaluations: 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.
Alphagan: In comparative clinical studies with timolol 0.5%, lasting up to one year, the IOP lowering effect of ALPHAGAN was approximately 4-6 mmHg compared with approximately 6 mmHg for timolol. 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.
Alphagan P 0.1%: A 3-month (with a double-masked extension to 1 year) clinical study (N=433) was conducted to evaluate the safety, efficacy, and acceptability of ALPHAGAN P 0.1% compared with ALPHAGAN 0.2% administered 3 times daily in patients with glaucoma or ocular hypertension.
A 3-month analysis of the pivotal study indicated that ALPHAGAN P 0.1% is equivalent in IOP-lowering effect to ALPHAGAN 0.2% and effectively lowers IOP in patients with glaucoma or ocular hypertension (mean change from baseline IOP -3.3 to -5.4 mmHg).
Additionally, 12-month analysis of the pivotal study indicated ALPHAGAN P 0.1% continued to be equivalent to ALPHAGAN 0.2% and effectively lowered IOP in patients with glaucoma or ocular hypertension (mean change from baseline IOP at hours 0, 2, and 8 ranged from -2.7 to -5.4 mmHg). ALPHAGAN P 0.1% is well-tolerated and provides a superior safety profile when compared with ALPHAGAN 0.2%. ALPHAGAN P 0.1% is the lowest effective dose of brimonidine tartrate that combines the IOP lowering efficacy with the most favorable safety and tolerability profile.