UNOPROSTONE

Absorption

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. mean peak unoprostone free acid plasma concentration was <1.5 ng/mL and dro pped below the lower limit of quantitation (<0.250 ng/mL) 1 hour following instillation, indicating low systemic absorption and rapid plasma excretion.

Toxicity

LD50 in rats: 1g/Kg (subcutaneous), 93500 μg/Kg (IV).

The Uses of UNOPROSTONE

Unoprostane is a protectant against retinal degeneration in S334ter rhodopsin mutant rats. Neuroprotective agent.

Indications

For the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another intraocular pressure lowering medication.

Background

Unoprostone isopropyl is a prostaglandin analogue. Ophthalmic Solution 0.15% is a synthetic docosanoid. Unoprostone isopropyl has the chemical name isopropyl (+)-(Z)-7-[(1R,2R,3R,5S)-3,5 dihydroxy-2-(3-oxodecyl)cyclopentyl]-5-heptenoate. The main indication of Unoprostane is treatment of glucoma.

What are the applications of Application

Unoprostone is a PGF2α analog

Definition

ChEBI: Unoprostone is an oxo monocarboxylic acid, a prostaglandins Falpha and a ketone. It has a role as an antiglaucoma drug and an antihypertensive agent.

General Description

Unoprostone (Rescula) is supplied as a 0.15% sterileophthalmic solution. Unoprostone is somewhat unusual inthat it is a docosanoid (22-carbon atom) PGF_2α analog marketedas the isopropyl ester. The natural 15-position alcoholis oxidized to the ketone as would be expected to occur invivo. Cautions and side effects are similar to those givenpreviously.

Pharmacokinetics

Unoprostone will begin to reduce IOP 30 minutes after ocular instillation.

Metabolism

After ocular application, unoprostone isopropyl is hydrolyzed by esterases in the cornea to its biological active metabolite, unoprostone free acid. Unoprostone free acid is then metabolized to several inactive metabolites with lower molecular weight and increased polarity via ε- or β-oxidation. No secondary conjugation is found and no significant effect on hepatic microsomal enzyme activity has been observed.