Isolation and identification of metabolites of ofloxacin in rats, dogs and monkeys

Abstract

1. Metabolites of (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (ofloxacin) in excreta of rats, dogs and monkeys after oral administration of ¹⁴C-ofloxacin (20 mg/kg) were isolated and identified.

2. Three metabolites of ofloxacin were detected in the excreta of all three species, and identified by t.l.c., u.v., n.m.r. and mass spectrometry as follows: M-1, ester glucuronide of ofloxacin; M-2, unchanged ofloxacin; M-3, (±)-9-fluoro-2,3-dihydro-3-methyl-10-(1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (desmethyl ofloxacin); M-4, (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylic acid piperazine-4-oxide (ofloxacin N-oxide).

3. It is concluded that ofloxacin is metabolized by O-acyl glucuronidation, N-demethylation and N-oxidation.