Abstract
The kinetics of serum concentrations, and the ototoxicity and nephrotoxicity of aminoglycoside antibiotics administered by intravenous infusion were studied in a total of 87 rabbits, and compared with those observed after administration by intramuscular injection.
(1) The serum concentratrations and urinary recovery rate of dibekacin (DKB) obtained after intravenous infusion over one-bour period were compared with those obtained by intramuscular injection. The results revealed that there was no significant difference in peak serum concentrations between intramuscular injection and intravenous infusion at doses of 100 and 50mg/kg. However, with DKB at 2mg/kg, a clinically used dosage, significant higher serum concentrations were attained after intramuscular injection than after intravenous infusion.
With respect to the area under the curve (AUC) or cumulative urinary recovery rate, no significant difference was seen between intramuscular injection and intravenous infusion for any of the dose levels.
(2) For the histopathological studies of the inner ear and the kidney, DKB was administered at three different dosages of 100, 50 and 30mg/kg either by intramuscular injection or by intravenous infusion, while gentamicin (GM) was administered at 50mg/kg by intramuscular route and at 30mg/kg by intramuscular and intravenous routes. These drugs were administered daily for 30 days. At 10 days after completion of the administration, animals were sacrificed and examined of the inner ear by the surface preparation technique with phase contrast microscopy. The kidney was observed after staining with H-E and PAS. Both inner ear damage and renal damage were less in DKB group than in GM group. However, no difference was seen in the severity and types of damage between animals receiving the drugs by intramuscular injection and those by intravenous infusion. From these results, it is considered that in terms of ototoxicity and nephro-toxicity, intravenous infusion of aminoglycoside antibiotics over one-hour period is almost equally safe as its intramuscular injection.
