N Bodor1, W M Wu, T Murakami, S Engel. 1. Center for Drug Discovery, J. Hillis Miller Health Center, College of Pharmacy, University of Florida, Gainesville 32610, USA.
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.
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.