PHARMACOKINETICS OF PRULIFLOXACIN .3. METABOLISM IN RATS, DOGS AND MONKEYS

The metabolism of the new quinolone antibacterial prodrug prulifloxaci n -oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid, CAS 123447- 62-1, NM441) in rats, dogs and monkeys was investigated after oral adm inistration of C-14-NM441 or unlabeled NM441. 1. NM394 (which is the a ctive metabolite of NM441), the NM394 acyl glucuronide, the ethylenedi amino form, the diol form and the amino form were found in the urine o f all three species, and the oxo form was detected in monkey urine onl y. 2. NM394 was the main metabolite in the urine of dogs and monkeys. 3. NM394 was the main metabolite in the plasma, urine and feces in rat s and NM394 and its acyl glucuronide were the main biliary metabolites . 4. These results indicate that NM441 was transformed into a variety of metabolites, but that most of the drug administered was metabolized to NM394 by hydrolytic cleavage of the dioxelene ring.