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Latanoprost is an ester prodrug analogue of prostaglandin F2α which effectively reduces intraocular pressure (IOP) by increasing uveoscleral outflow rather than altering conventional (trabeculo-canalicular) aqueous outflow. The IOP-lowering effect of latanoprost lasts for 20 to 24 hours after a single dose, which allows a single daily dosage regimen.
Data from 4 randomised double-masked multicentre studies indicate that a once daily dose of topical latanoprost 0.005% is as effective as timolol 0.5% twice daily in the treatment of patients with primary open-angle glaucoma or ocular hypertension. A number of studies also demonstrate that latanoprost enhances IOP-lowering effects when applied in combination with other antiglaucoma agents.
Latanoprost is well tolerated with no, or barely detectable, conjunctival hyperaemia, and, unlike timolol, is not associated with systemic adverse effects. However, 3 to 10% of patients treated with latanoprost 0.005% have shown increased iris pigmentation after 3 to 4.5 months’ treatment.
In summary, the available data show that latanoprost is a potent IOP-lowering agent with a number of positive features including a single daily dosage regimen, a novel mechanism of action that enhances the IOP-lowering effect of contemporary agents, and a lack of systemic adverse effects. These properties suitably poise latanoprost for a prominent position in the management of patients with primary open-angle glaucoma and ocular hypertension.
Latanoprost is an ester prodrug analogue of prostaglandin F2α with high selectivity for the FP subtype of prostanoid receptors. Unlike contemporary antiglaucoma agents, latanoprost reduces intraocular pressure (IOP) by increasing uveoscleral outflow, with little or no alteration of conventional (trabeculo-canalicular) aqueous outflow and no effects on retinal vasculature or permeability of the blood-aqueous barrier.
The reduction in IOP produced by latanoprost is dose-dependent. The IOP-lowering effects after a single dose of latanoprost 0.006% last for up to 20 to 24 hours. Long term (6 months) application of latanoprost is not associated with morphological alterations to the ciliary muscle or trabecular meshwork, according to animal data. Furthermore, other body systems (brain, cardiovascular, respiratory) do not appear to be significantly affected by latanoprost at concentrations up to 10-fold greater than those used clinically for topical application.
Latanoprost is more lipophilic than its parent prostaglandin and therefore better able to penetrate the cornea. After uptake by the cornea, latanoprost is completely hydrolysed; the drug does not seem to be metabolised by other means in the eye. In monkeys, the highest drug concentrations were observed in the cornea after topical administration; the acid of latanoprost was then released from the cornea into the anterior eye. The drug had an elimination half-life of 3 to 4 hours from the eye tissues.
Drug that is systemically absorbed has a short plasma elimination half-life. The major metabolic pathway is by β-oxidation and the metabolites are excreted primarily via the kidneys. Recovery of radiolabelled drug appears to be complete.
Dose-ranging studies show that a once daily topical dose of latanoprost (optimal concentration of 0.005 or 0.006%) effectively produces a decrease in IOP in patients with primary open-angle glaucoma or ocular hypertension. Single daily application of latanoprost is at least as effective as a twice daily dose.
Three of 4 long term (3 or 6 months) randomised, double-masked, multicentre studies indicated that once daily latanoprost 0.005% was more effective than timolol 0.5% twice daily in reducing IOP. A number of clinical studies have also shown that latanoprost applied in combination with other antiglaucoma agents produces enhanced IOP-lowering effects.
Data from phase III clinical studies indicate that topical latanoprost 0.005% once daily application is, overall, as well tolerated as timolol 0.5% twice daily. At clinically effective doses, no or a barely detectable increase in conjunctival hyperaemia was noted in at least 90% of latanoprost or timolol recipients. In contrast to timolol, latanoprost is not associated with systemic adverse effects.
On the other hand, increased iridial pigmentation has been noted in 3 to 10% of patients after 3 to 4.5 months’ continuous treatment with latanoprost 0.005%. It occurred only in patients with mixed colour irises (green-brown or blue/grey-brown); freckles or naevi in the iris were not affected.
Dosage and Administration
Once-daily topical instillation of latanoprost 0.005% is the recommended dosage regimen for the treatment of patients with primary open-angle glaucoma or ocular hypertension. If used in combination with other topical antiglaucoma agents, the drugs should be instilled at least 5 minutes apart.
KeywordsGlaucoma Intraocular Pressure Timolol Latanoprost Ocular Hypertension
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