[Biotransformation of selected gyrase inhibitors]

The common structure of the gyrase inhibitors norfloxacin, ciprofloxacin, pefloxacin, and ofloxacin is 3-carboxy-4-oxo-6-fluoro-7-(1-piperazinyl)-1,4-dihydro-quinolone. Several biotransformations of these substances are reported in the literature, mostly in animals and partly in humans: 1. Conjugation of the carboxylic acid to glucuronic acid (formation of an O-methyl ester of norfloxacin was found only in the rat); 2. Oxidation of the piperazine ring to the oxo derivative and subsequent metabolisation (or degradation) of the piperazine ring to several intermediates and finally to elimination of the side chain; 3. Substitution of the piperazine side chain to the 4-N-acetyl or 4-N-formyl-derivative (norfloxacin, ciprofloxacin); 4. Methylation of the 4-methyl-piperazine side chain (pefloxacin, ofloxacin). 5. N-oxidation of the 4-methyl-piperazine side chain (pefloxacin, ofloxacin). The glucuronides are microbiologically inactive. The activity of metabolites with a modified piperazine side chain varies from high (oxo derivatives) to low (after splitting of the ring). Quantitative data on the formation of the described transformation products in humans are presently still incomplete. The oxo derivative appears to be the main metabolite of norfloxacin and ciprofloxacin. Additional metabolites to the described ones are likely to be detected in the near future.