Source: FDA, National Drug Code (US)
When instilled in the eye, RESCULA is believed to reduce elevated intraocular pressure (IOP), by increasing the outflow of aqueous humor, but the exact mechanism is unknown at this time.
After application to the eye, unoprostone isopropyl is absorbed through the cornea and conjunctival epithelium where it is hydrolyzed by esterases to unoprostone free acid.
A study conducted with 18 healthy volunteers dosed bilaterally with unoprostone isopropyl ophthalmic solution twice daily for 14 days demonstrated little systemic absorption of unoprostone isopropyl. The systemic exposure of its metabolite unoprostone free acid was minimal following the ocular administration. Mean peak unoprostone free acid concentration was less than 1.5 ng/mL. Little or no accumulation of unoprostone free acid was observed.
Elimination of unoprostone free acid from human plasma is rapid, with a half-life of 14 minutes. Plasma levels of unoprostone free acid dropped below the lower limit of quantitation (<0.25 ng/mL) 1 hour following ocular instillation. The metabolites are excreted predominately in urine.
Clinical studies showed that in patients with mean baseline IOP of 23 mm Hg, RESCULA lowers intraocular pressure by approximately 3-4 mm Hg throughout the day. RESCULA appears to lower intraocular pressure without affecting cardiovascular or pulmonary function.
Rescula was not carcinogenic in rats administered oral doses up to 12 mg/kg/day for up to 2 years (approximately 580 and 240 fold the recommended human dose of 0.005 mg/kg/day based on AUC0-24 in male and female rats, respectively).
Under the conditions tested, unoprostone isopropyl and unoprostone free acid were neither mutagenic in an Ames assay nor clastogenic in a chromosome aberration assay in Chinese hamster lung-derived fibroblast cells. Under the conditions tested, unoprostone isopropyl was not genotoxic in a mouse lymphoma mutation assay or clastogenic in an in vivo chromosomal aberration test in mouse bone marrow.
Unoprostone isopropyl did not impair male or female fertility in rats at subcutaneous doses up to 50 mg/kg (approximately 10,000 fold the recommended human dose of 0.005 mg/kg/day).
In cynomolgus monkeys administered Rescula for twelve months at 150 µg/eye/day (equal to the human dose), one of ten animals exhibited increased pigmentation of the iris. The incidence did not change when the administered dose was increased to 300 µg/eye/day (twice the human dose) for an additional six months.
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