Soft drugs. 19. Pharmacokinetics, metabolism and excretion of a novel soft corticosteroid, loteprednol etabonate, in rats.
OBJECTIVE
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.
Bodor
N
N
Center for Drug Discovery, J. Hillis Miller Health Center, College of Pharmacy, University of Florida, Gainesville 32610, USA.
Wu
W M
WM
Murakami
T
T
Engel
S
S
D000730:Androstadienes / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D000069559:Loteprednol Etabonate; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000069559:Loteprednol Etabonate