FAILURE TO DETECT SYSTEMIC LEVELS, AND EFFECTS OF LOTEPREDNOL ETABONATE AND ITS METABOLITE, PJ-91, FOLLOWING CHRONIC OCULAR ADMINISTRATION

The objective of this study was to determine the systemic exposure to loteprednol etabonate (LE) following its chronic, ocular instillation. This was a randomized, double-masked, placebo controlled, single cent er trial in 14 normal volunteers. Subjects were randomly assigned to r eceive either LE (n = 10) or placebo (n = 4) and instructed to instill one drop into each eye 8 times daily on Days 0 and 1 and four times d aily on Days 2 through 42. Blood levels of loteprednol etabonate (LE) and its major metabolite PJ-91 (Delta(1) cortienic acid etabonate) in plasma, and circulating plasma cortisol levels were measured during th e study. Plasma levels of LE or PJ-91 were below the level of quantita tion (1 ng/mL) for all subjects in both treatment groups. Plasma corti sol levels were all within the normal range. Chronic exposure to LE at a concentration and frequency equal to or greater than the intended t herapeutic dose does not result in detectable systemic levels or hypot halamic pituitary axis suppression.