Abstract
Purpose. Pharmacokinetics, metabolism and excretion of loteprednol etabonate (LE) were investigated in rats.
Methods. The pharmacokinetic studies were performed by iv injections of LE (1-20 mg/ kg). In the metabolism and excretion studies, 0.5-10 mg/kg of LE were iv administered, bile and urine samples were collected for 6 hr.
Results. The pharmacokinetic of LE showed a rapid, dose-dependent elimination with a total blood clearance (CLtotal) of higher than 60 ml/min/kg. The metabolism and excretion of LE also showed a marked dose-dependency. At 6 hr after iv of LE (0.5-10 mg/kg), the total recoveries (LE and the metabolites, AE & A, in bile and urine) were 99.35-26.72%. However, only about 2% of LE was excreted from the body through the urine. There were 0.93-2.12% and 0.66-0.26% of AE, and 75.67-19.69% and 20.74-2.77% of A excreted in the bile and urine, respectively. The excretion of A was dose dependent, and significantly higher at the lower dose. Using the (% of total excretion) vs. (log dose) plots, it could be predicted that almost all of the administered LE will be metabolized, and excreted as A when the systemic dose is lower than 0.25 mg/kg.
Conclusions. The results indicate that LE absorbed systemically, after topical administration, can be rapidly transformed to the inactive metabolites, and eliminated from the body mainly through the bile and urine.
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Bodor, N., Wu, WM., Murakami, T. et al. Soft Drugs 19. Pharmacokinetics, Metabolism and Excretion of a Novel Soft Corticosteroid, Loteprednol Etabonate, in Rats. Pharm Res 12, 875–879 (1995). https://doi.org/10.1023/A:1016265105139
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DOI: https://doi.org/10.1023/A:1016265105139