Apraclonidine hydrochloride is a relatively selective alpha-2-adrenergic agonist. When instilled in the eye, apraclonidine ophthalmic solution has the action of reducing elevated, as well as normal, intraocular pressure (IOP), whether or not accompanied by glaucoma. Ophthalmic apraclonidine has minimal effect on cardiovascular parameters. 

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. Apraclonidine ophthalmic solution has the action of reducing IOP. The onset of action of apraclonidine can usually be noted within one hour, and maximum IOP reduction occurs about three hours after instillation. Aqueous fluorophotometry studies demonstrate that apraclonidine's predominant mechanism of action is reduction of aqueous flow via stimulation of the alpha-adrenergic system. 

Repeated dose-response and comparative studies (0.125% to 1.0% apraclonidine) demonstrate that 0.5% apraclonidine is at the top of the dose/response IOP reduction curve. 

The clinical utility of apraclonidine ophthalmic solution is most apparent for those glaucoma patients on maximally tolerated medical therapy. Patients on maximally tolerated medical therapy with uncontrolled IOP and scheduled to undergo laser trabeculoplasty or trabeculectomy surgery were enrolled into a double-masked, placebo-controlled, multi-center clinical trial to determine if apraclonidine ophthalmic solution, dosed three times daily, could delay the need for surgery for up to three months. 

All patients enrolled into this trial had advanced glaucoma and were undergoing maximally tolerated medical therapy, i.e., patients were using combinations of a topical beta blocker, sympathomimetics, parasympathomimetics and oral carbonic anhydrase inhibitors. Patients were considered to be treatment failures in this study if, in the opinion of the investigators, their IOP was uncontrolled by the masked study medication or there was evidence of further optic nerve damage or visual field loss, and surgery was indicated. Of 171 patients receiving masked medication, 84 were treated with apraclonidine ophthalmic solution and 87 were treated with placebo (apraclonidine vehicle). 

Apraclonidine treatment resulted in a significantly greater percentage of treatment successes compared to patients treated with placebo. In this placebo-controlled maximum therapy trial, 14.3% of patients treated with apraclonidine ophthalmic solution were discontinued due to adverse events, primarily allergic-like reactions (12.9%). 

The IOP lowering efficacy of apraclonidine ophthalmic solution diminishes over time in some patients. This loss of effect, or tachyphylaxis, appears to be an individual occurrence with a variable time of onset and should be closely monitored. 

An unpredictable decrease of IOP control in some patients and incidence of ocular allergic responses and systemic side effects may limit the utility of apraclonidine ophthalmic solution. However, patients on maximally tolerated medical therapy may still benefit from the additional IOP reduction provided by the short-term use of apraclonidine ophthalmic solution. 

Topical use of apraclonidine ophthalmic solution leads to systemic absorption. Studies of apraclonidine ophthalmic solution dosed one drop three times a day in both eyes for 10 days, in normal volunteers, yielded mean peak and trough concentrations of 0.9 ng/mL and 0.5 ng/mL, respectively. The half-life of apraclonidine ophthalmic solution was calculated to be 8 hours. 

Apraclonidine ophthalmic solution, because of its alpha adrenergic activity, is a vasoconstrictor. Single dose ocular blood flow studies in monkeys, using the microsphere technique, demonstrated a reduced blood flow for the anterior segment; however, no reduction in blood flow was observed in the posterior segment of the eye after a topical dose of apraclonidine ophthalmic solution. Ocular blood flow studies have not been conducted in humans.