Metabolism and nephrotoxicity of phenacetin and sulfanilamide.

Publisher Website
Google Scholar
Abstract
The mechanism of renal damage produced by sulfanilamide and phenacetin were studied. N-Hydroxyphenacetin, 4-hydroxylaminobenzenesulfonamide (4-HABSA) and p-aminophenol were established to be nephrotoxic metabolites. As well as N-hydroxylase activity of sulfanilamide, that of phenacetin in kidney microsomes of rats was increased about 4 times by pretreatment with 3, 4, 5, 3'', 4''-pentachlorobiphenyl (PenCB) which is a potent inducer of cytochrome P-448. Parallel to this enzyme induction, pretreatment with PenCB enhanced the nephrotoxicity of phenacetin and sulfanilamide in rats. The formation of p-aminophenol from phenacetin was also confirmed in rat kidney in vitro. 4-HABSA, N-hydroxyphenacetin and p-aminophenol formed in kidney apparently play an important role in the renal damage produced by sulfanilamide and phenacetin.