DOSE-RELATED EFFECTS OF PROSTAGLANDIN-F2-ALPHA ISOPROPYLESTER ON INTRAOCULAR-PRESSURE, REFRACTION, AND PUPIL DIAMETER IN MONKEYS

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-mu-g had smaller and less consistent but longer lasting IOP-lowering effects than repeated doses (twice daily for 3 days) of 1-5-mu-g. For repeated dosing in this manner, the just-maximal dose is probably between 2-5-mu-g, 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-mu-g dose. Partial reversal of anesthesia-induced tonic accommodation occurred with single 10- and 30-mu-g doses and with repeated 1-mu-g 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.