Failure to detect systemic levels, and effects of loteprednol etabonate and its metabolite, PJ-91, following chronic ocular administration

J Ocul Pharmacol Ther. 1998 Apr;14(2):153-8. doi: 10.1089/jop.1998.14.153.


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 center trial in 14 normal volunteers. Subjects were randomly assigned to receive 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 daily on Days 2 through 42. Blood levels of loteprednol etabonate (LE) and its major metabolite PJ-91 (delta1 cortienic acid etabonate) in plasma, and circulating plasma cortisol levels were measured during the study. Plasma levels of LE or PJ-91 were below the level of quantitation (1 ng/mL) for all subjects in both treatment groups. Plasma cortisol levels were all within the normal range. Chronic exposure to LE at a concentration and frequency equal to or greater than the intended therapeutic dose does not result in detectable systemic levels or hypothalamic pituitary axis suppression.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Androstadienes / administration & dosage*
  • Androstadienes / blood
  • Androstadienes / pharmacokinetics*
  • Double-Blind Method
  • Female
  • Humans
  • Hydrocortisone / blood
  • Loteprednol Etabonate
  • Male
  • Middle Aged
  • Ophthalmic Solutions
  • Time Factors


  • Androstadienes
  • Ophthalmic Solutions
  • PJ 91 compound
  • Hydrocortisone
  • Loteprednol Etabonate