Abstract
Summary
Isosorbide is an oral osmotic agent which lowers intraocular pressure in rabbits and man. To determine its possible accumulation in the eye after repeated administration, male rabbits were orally dosed with isosorbide, 2 g/kg, daily for from 1 to 7 days. Plasma and ocular components were removed from 1 to 24 hr after the last dose. After single or multiple doses of isosorbide, times to peak level and excretion half-lives (T 1/2) were similar for all tissues except the lens. Times to peak drug levels were: plasma, 1.1 hr; aqueous, vitreous, iris, and cornea, 1.3–1.5 hr; lens, 3.5 hr. Plasma T 1/2 (5.0 hr) was not different from that for lens (5.4 hr) but was significantly longer than T 1/2 for other ocular tissues. Further, average drug levels in plasma and all ocular tissues declined to the same low levels (< 0.20 mg/ml or mg/g) 24 hr after either a single dose or the last of several doses; thus, indicating no accumulation with 24-hr dose intervals. There were no differences in drug kinetics between normal eyes and eyes damaged with detergent treatment except that lens T 1/2 was shorter and isosorbide reached a peak level sooner in lenses from damaged eyes.
We thank Mr. J. P. Pollock, Jr., for performing GLC analysis; Mrs. J. F. May, for assistance with dosing and animal handling; and Mr. S. J. Rzucidlo for installation of detergent and grading of rabbit eyes. We are also indebted to the Safety Evaluation Section, Medical Research Department, for histologic examination of eyes.
Get full access to this article
View all access options for this article.