Lack of in vivo evidence of a cytochrome P450 metabolite participating in aminoglycoside nephrotoxicity.
Recent in vitro evidence has suggested that the cytotoxicity of aminoglycosides may be mediated by a metabolite generated by the hepatic cytochrome P450 drug-metabolizing system. This postulate has been tested by pretreating rats with cobalt protoporphyrin IX (CoP) to suppress hepatic P450 levels prior to administration of gentamicin. CoP pretreatment was observed to suppress antipyrine clearance markedly but not to alter gentamicin nephrotoxicity.
Sanders
T W
TW
Department of Comparative Medicine, Medical University of South Carolina, Charleston 29403-5833.
Reinhard
M K
MK
Jollow
D J
DJ
Hottendorf
G H
GH
D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005839:Gentamicins / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005839:Gentamicins; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine