Difloxacin

Difloxacin (INN), marketed under the trade name Dicural, is a second-generation, synthetic fluoroquinolone antibiotic used in veterinary medicine. It has broad-spectrum, concentration dependent, bactericidal activity; however, its efficacy is not as good as enrofloxacin or pradofloxacin. Difloxacin (INN), marketed under the trade name Dicural, is a second-generation, synthetic fluoroquinolone antibiotic used in veterinary medicine. It has broad-spectrum, concentration dependent, bactericidal activity; however, its efficacy is not as good as enrofloxacin or pradofloxacin. In 1997, the United States Food and Drug Administration approved difloxacin hydrochloride tablets for use in canines. Unlike other fluoroquinolones difloxacin has not been approved by the FDA for use in cats. It is also contraindicated for use in food animals. The recommended dosing is 5–10 mg/kg once daily. This is based on the linear pharmacokinetics exhibited by difloxacin over the 5–60 mg/kg range. So the maximum dose is well within the established safety range, but drug accumulation in tissues prompts a recommendation that the medication should not be used for periods longer than thirty days. If there is no noticeable improvement after five days, then the condition should be reevaluated and all therapy options reconsidered. Difloxacin is indicated for infections caused by susceptible microorganisms in the conditions listed below. Difloxacin is a bactericidal, broad-spectrum antibiotic that has activity against Gram-negative bacteria and Gram-positive bacteria. It exerts its antibacterial effect by interfering with the bacterial enzyme DNA gyrase, which is needed for the maintenance and synthesis of bacterial DNA. The minimum inhibitory concentrations (MICs) of pathogens isolated in clinical field trials conducted in the United States between 1991 and 1993 were determined using National Committee for Clinical Laboratory Standards (NCCLS). The primary mode of action of fluoroquinolones involves interaction with enzymes essential for major DNA functions such as replication, transcription and recombination. Difloxacin inhibits DNA gyrase (also known as Topoisomerase II), an enzyme required for negative super coiling during DNA replication Cell death can occur through the inability of bacteria to maintain the DNA super helical structure. Difloxacin is rapidly and almost completely absorbed after oral administration, and approximately 50% is bound to circulating plasma proteins. It is metabolized primarily by the liver through glucuronidation and secreted in the bile. It can also be reabsorbed with the bile. This allows reentry into the blood stream and recirculation, a mechanism that can extend the half-life. The longer half-life allows for once daily dosing. In contrast to other fluoroquinolones, renal clearance accounts for only 5% of the removal of difloxacin from the canine system, which makes it an attractive choice for dogs with compromised renal function. aTotal body clearance/F = Dose/AUC bSteady state volume of distribution/F = Dose•AUMC/AUC2 cVolume of distribution (area)/F = Vdβ = (T1/2)(CL/F)/0.693