title: Dose-related effects of prostaglandin F2 alpha isopropylester on intraocular pressure, refraction, and pupil diameter in monkeys.
abstract: Topical application of Prostaglandin F2 alpha (PGF2 alpha) to the eye reduces intraocular pressure (IOP) in all mammalian species studied thus far, including humans. The L-isopropylester derivative is currently the one most commonly used in experimental and clinical studies. Dose-response relationships were determined between PGF2 alpha-IE and IOP, pupillary diameter, and refraction in ketamine-anesthetized ocular normotensive cynomolgus monkeys. Single doses of 10 and 30 micrograms had smaller and less consistent but longer lasting IOP-lowering effects than repeated doses (twice daily for 3 days) of 1-5 micrograms. For repeated dosing in this manner, the just-maximal dose is probably between 2-5 micrograms, producing a approximately 70% reduction in IOP to a final IOP of approximately 5 mm Hg. Continuing treatment for up to 18 days did not further enhance the efficacy of twice daily treatment with a submaximal 1-microgram dose. Partial reversal of anesthesia-induced tonic accommodation occurred with single 10- and 30-micrograms doses and with repeated 1-microgram doses, but additional myopia of 0.5-1.5 diopters was induced with repeated higher doses. These physiologic findings and previous morphologic data are consistent with a proposed dual PG action on the ciliary muscle, one involving a short-onset long-lasting direct effect on the muscle fibers (causing relaxation and narrowing of the muscle bundles) and the second involving a slowly developing but shorter duration dissolution of the intermuscular connective tissues.
authors.affiliation: Department of Ophthalmology, University of Wisconsin, Madison.
authors.forename: K S
authors.initials: KS
authors.lastname: Crawford
authors.forename: P L
authors.initials: PL
authors.lastname: Kaufman
mesh_terms: D000065:Accommodation, Ocular / Q000187:drug effects*; D000818:Animals; D015237:Dinoprost / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D007498:Iris / Q000033:anatomy & histology / Q000187:drug effects; D008252:Macaca fascicularis; D011680:Pupil / Q000187:drug effects*; D012029:Refraction, Ocular
chemical_list: C041158:prostaglandin F2 isopropyl ester; D015237:Dinoprost