PHARMACOKINETIC PARAMETERS OF NETILMICIN AND PROTECTIVE EFFECT OF PIPERACILLIN REGARDING NEPHROTOXICITY CAUSED BY NETILMICIN

The pharmacokinetic interaction of Netilmicin and Piperacillin has bee n studied as well as the potential protective effect that Piperacillin exert on nephrotoxicity caused by Netilmicin, when both antibiotics a re administered to rabbits by single and multiple dosage regimens. Net ilmicin was administered at a dose of 7 mg/kg and 12 h interval, which allometrically correspond to 5 mg/kg at 24 h interval for men. Pipera cillin was administered at a dose of 280 mg/kg at 12 h interval (the t otal number of doses of both antibiotics was 20). After single and mul tiple dose regimens plasma level curves of Netilmicin and renal concen tration were determined using an HPLC technique. Besides that, an hist ologic study was carried out by electronic microscopy to determine the renal damage. A significant variation of some pharmacokinetic paramet ers of Netilmicin such as Vc and tin was observed when Netilmicin is a dministered together with Piperacillin; a similar modification in the renal accumulation and renal damage caused by Netilmicin was shown.