Mechanism of Action
Latanoprost is a prostanoid selective FP receptor agonist that is believed to reduce
the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Studies
in animals and man suggest that the main mechanism of action is increased uveoscleral
outflow. Elevated IOP represents a major risk factor for glaucomatous field loss.
The higher the level of IOP, the greater the likelihood of optic nerve damage and
visual field loss.
Pharmacokinetics/Pharmacodynamics
Absorption: Latanoprost is absorbed through the cornea where the isopropyl
ester prodrug is hydrolyzed to the acid form to become biologically active. Studies
in man indicate that the peak concentration in the aqueous humor is reached about
two hours after topical administration.
Distribution: The distribution volume in humans is 0.16 ± 0.02 L/kg. The
acid of latanoprost can be measured in aqueous humor during the first 4 hours, and
in plasma only during the first hour after local administration.
Metabolism: Latanoprost, an isopropyl ester prodrug, is hydrolyzed by esterases
in the cornea to the biologically active acid. The active acid of latanoprost reaching
the systemic circulation is primarily metabolized by the liver to the 1,2-dinor
and 1,2,3,4-tetranor metabolites via fatty acid β-oxidation.
Excretion: The elimination of the acid of latanoprost from human plasma is
rapid (t1/2=17 min) after both intravenous and topical
administration. Systemic clearance is approximately 7 mL/min/kg. Following hepatic
β-oxidation, the metabolites are mainly eliminated via the kidneys. Approximately
88% and 98% of the administered dose is recovered in the urine after topical and
intravenous dosing, respectively.
Animal Studies
In monkeys, latanoprost has been shown to induce increased pigmentation of the iris.
The mechanism of increased pigmentation seems to be stimulation of melanin production
in melanocytes of the iris, with no proliferative changes observed. The change in
iris color may be permanent.
Ocular administration of latanoprost at a dose of 6 µg/eye/day (4 times the daily
human dose) to cynomolgus monkeys has also been shown to induce increased palpebral
fissure. This effect was reversible upon discontinuation of the drug.