Therapeutic Review Enrofloxacin

Enrofloxacin is a member of the family of 6-fluoro-7-piperazinyl-4-quinolones.1 This antibiotic is highly lipophilic, and the addition of a carboxic acid and a tertiary amine contributes to the amphoteric properties of enrofloxacin.2 Enrofloxacin is bactericidal and has excellent activity against both Gram-positive and Gram-negative pathogens.1,3 This antibiotic has also been used to control certain intracellular pathogens. Modification of the 4-quinolone ring has enhanced the antimicrobial activity of this compound. Oral bioavailability of enrofloxacin is excellent in monogastric mammals and preruminant calves, with up to 80% of the ingested dose being absorbed into systemic circulation.2 Oral absorption of enrofloxacin is rapid, with peak serum concentrations achieved 1 to 2 hours after administration.4 Enrofloxacin does not readily complex with plasma proteins, which enables metabolites to readily cross cell membranes. In humans, approximately 10% to 40% of the fluoroquinolones are bound to plasma proteins.2 As a group, the fluoroquinolones are widely distributed throughout the body, including the kidneys, liver, bile, prostate, uterus and fallopian tubes, bone, and inflammatory tissues.5 Excretion of the fluoroquinolones is primarily through the kidneys, with secondary excretion through the liver.2,5 Enrofloxacin alters the action of bacterial DNA gyrase, a type II topoisomerase.2 This enzyme is involved in unwinding, cutting, and resealing DNA. There are two subunits to DNA gyrase: subunit A and subunit B. Enrofloxacin acts on the nalA locus of subunit A. Inhibition of the gyrase leads to rapid cell death in bacteria. The concentration of fluoroquinolones required to alter the DNA of mammalian cells is two orders of magnitude higher than the concentration against bacterial DNA.6,7 The metabolism of enrofloxacin varies between species. Although enrofloxacin is an active antibiotic, biotransformation to ciprofloxacin may occur in some species. Biotransformation of enrofloxacin includes N-dealkylation, glucuronide conjugation to the nitrogen in the para position of the piperazinyl