Its advantages included having low nephrotoxicity and effectiveness with only once daily dosing in the treatment of numerous infections.2,3) Since fleroxacin is often combined with isepamicin, and this combination has been shown to be very effective as a first-line antibiotic combination in the treatment of severe infections, the potential of additive nephrotoxicity in the fleroxacin isepamicin combination regimen is of great clinical importance.Different compounds or drugs used concomitantly with aminoglycosides may either increase or decrease aminoglycoside toxicity. In fact, drugs such as cisplatinum 4) and vancomycin 5) increase the nephrotoxicity of aminoglycosides, while recent studies showed that poly-L-aspartic acid, 6) daptomycin, 7,8) carbenicillin, 9) ticarcillin 10) and ceftriaxone 11) protected the kidney against aminoglycoside-induced nephrotoxicity.Fleroxacin is a synthetic broad-spectrum antibiotic belonging to the class of fluoroquinolones.12) It shows good antibacterial activity against many gram-negative bacteria, and less activity against gram-positive bacteria. 13,14) A recent investigation showed that fleroxacin (intraperitoneally) protected against gentamicin-induced nephrotoxicity in rats when both drugs were administered in combination. 15) In Japan, fleroxacin is given orally. In rats, fleroxacin reaches peak serum levels within 1 h after oral administration, with a half-life of 2.3 h. 16) In contrast with several other quinolones, fleroxacin is not metabolized and is mainly excreted unchanged in the urine.14,17,18) Fleroxacin reaches peak kidney concentrations within 0.5-1 h. In fact, high concentrations of fleroxacin have been measured in the kidney of rabbits 19) and in the human kidneys. 20) Moreover, the accumulation of fleroxacin was higher in the kidneys of patients with symptomatic complicated urinary tract infections.
21)To our knowledge, there are no data on the effects of fleroxacin (orally) on the nephrotoxicity of administered isepamicin. In view of the particular distribution of fleroxacin within the kidney, we have evaluated the nephrotoxic potential of the fleroxacin (orally) isepamicin combination regimen.
MATERIALS AND METHODSAdult male Wistar rats weighing between 130-150 g were used. The animals were housed in a light-controlled room (lights on from 0800 to 2000 h) at a room temperature of 24Ϯ1°C and humidity of 60Ϯ10% for 1 week. They were acclimated for one week, and they had free access to food and water throughout the experiment.Isepamicin was dissolved in saline (0.9% NaCl). Fleroxacin was suspended in 0.3% sodium carboxymethyl cellulose (CMC-Na).For 14 d, animals were given one of the 4 regimens: a single injection of either saline (intraperitoneally) and CMC-Na (orally), saline (intraperitoneally) and fleroxacin 100 mg/kg (orally), isepamicin 300 mg/kg (intraperitoneally) and CMCNa (orally) or isepamicin (intraperitoneally) with fleroxacin (orally) at the same dose as when used alone. Animals were injected at 1300 h. This dosing schedule was determined from ...
