Characteristics. Colorless or slightly yellowish oil. Easily soluble in acetonitrile, soluble in acetone, ethanol, central distributing ethyl acetate, isopropanol, methanol and octanol, central distributing practically insoluble in water. Pharmacology.
Analogue PHF2alfa central distributing selective agonist PROSTANOID FP-receptor. central distributing It lowers intraocular pressure due to increased outflow of aqueous humor, mostly uveoskleralnoho. May gradually change central distributing eye color, central distributing increasing the amount of brown pigment in the iris by increasing the number of melanosomes (pigment granules) in melanocytes of the iris stroma. Typically, the brown pigmentation, which is located around the pupil spreads toward the periphery of the iris of the eye affected, but perhaps solid brown color of the iris or just its parts. During treatment central distributing may increase the severity of freckles on the iris. Change the color of the iris is slow and may be unnoticed for months or years. Pigmentation of the iris may be more pronounced in patients with green-brown holubo- / gray-korichnevyy central distributing or yellow-brown eyes. In clinical trials brown color of the iris does not progress after discontinuation of therapy, but may be irreversible. The effect on melanocytes and / or deposition of pigment granules in other parts of the eye during prolonged use is not currently known. Latanoprost may cause darkening of the eyelid skin and gradually change eyelashes and vellus hair. Showed an increase in the length, thickness and pigmentation of eyelashes, and violation of the right direction of growth of eyelashes (these changes may be irreversible). Effect of latanoprost on the corneal endothelium after prolonged use insufficiently studied.
According to a multicenter, randomized, central distributing controlled central distributing trials in patients with baseline intraocular pressure (IOP) 24-25 mmHg, latanoprost treated for 6 months, was shown to reduce intraocular pressure by 6-8 mmHg Lowering IOP begins 3-4 hours after instillation and reaches a peak after 8-12 h significant differences central distributing in safety or efficacy of latanoprost central distributing in patients younger and older were found.
Latanoprost at instillation absorbed through the cornea where the isopropyl ester (prodrug) is hydrolyzed by esterases to the cornea acid has biological activity. Peak concentrations in watery moisture is reached in 2 hours after application. The volume of distribution is 0,16 0,02 l / kg. Acid of latanoprost on intraocular fluid is determined during the first 4 h plasma - only during the first hour after topical application. central distributing Active acidic form, which reached systemic blood flow, primarily metabolized in the liver by beta-oxidation of fatty acid to 1,2-Dinora-and-1,2,3,4-tetranor metabolites. T1 / 2 of plasma latanoprost acid after the / in the introduction and local instillation of 17 minutes. Systemic clearance - about 7 ml / min / kg. The metabolites central distributing are excreted mainly by the kidneys, about 88% and 98% received central distributing dose appears in the urine at the local and / or to the administration respectively.
Studies in monkeys noted increased pigmentation of the iris - an undesirable effect associated with proliferation of melanocytes not, and with the stimulation of melanin production in melanocytes of the iris stroma. In the study of latanoprost ophthalmic toxicity monkeys administered at a dose of 6 mg / eye / day (4-fold excess of daily human dose) and caused an increase in the optic fissure. This effect was reversible and occurred by exceeding the standard central distributing therapeutic doses.
In studies on cultures central distributing of bacteria cells lymphomas in mice and micronucleus test in mice mutagenic properties were found. Chromosomal aberrations observed in in vitro studies in human lymphocytes. In tests on mice and rats treated with latanoprost orally at a dose of 170 mg to / kg / day (approximately 2800 times the recommended for a person) for 20 and 24 months respectively carcinogenic properties have been identified. Additional studies in vitro and in vivo in rats unscheduled DNA synthesis was found. Studying the impact central distributing of latanoprost on fertility revealed no changes in female and male animals. Application.
According to the Physicians Desk Reference (2008), latanoprost is indicated for elevated intraocular pressure in patients with open-angle glaucoma and ocular hypertension, including with tolerance to other IOP lowering drugs or lack of effectiveness. Contraindications.
Pregnancy, breastfeeding, child age (safety and efficacy not established); active inflammation in the eyeball (iritis, uveitis), aphakia, psevdoafakiya to damage the lens capsule, state, accompanied by the risk of macular edema, angle-closure glaucoma central distributing with signs of inflammation central distributing or neovascularization, wearing contact lenses, liver damage and kidney. Side effects.
According multicenter, double-blind, controlled trials in 5-15% of patients treated with latanoprost for 6 months, marked a noticeabl