Pharmacokinetic parameters of netilmicin and protective effect of piperacillin regarding nephrotoxicity caused by netilmicin.
The pharmacokinetic interaction of Netilmicin and Piperacillin has been studied as well as the potential protective effect that Piperacillin exert on nephrotoxicity caused by Netilmicin, when both antibiotics are administered to rabbits by single and multiple dosage regimens. Netilmicin 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. Piperacillin was administered at a dose of 280 mg/kg at 12 h interval (the total number of doses of both antibiotics was 20). After single and multiple dose regimens plasma level curves of Netilmicin and renal concentration were determined using an HPLC technique. Besides that, an histologic study was carried out by electronic microscopy to determine the renal damage. A significant variation of some pharmacokinetic parameters of Netilmicin such as Vc and t(1/2) was observed when Netilmicin is administered together with Piperacillin; a similar modification in the renal accumulation and renal damage caused by Netilmicin was shown.
Santos Navarro
M
M
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Spain.
Zarzuelo Castañeda
A
A
López
F G
FG
Sánchez Navarro
A
A
Arévalo
M
M
Lanao
J M
JM
D000818:Animals; D005839:Gentamicins / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009428:Netilmicin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity; D010406:Penicillins / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011817:Rabbits
D005839:Gentamicins; D010406:Penicillins; D020011:Protective Agents; D009428:Netilmicin; D010878:Piperacillin