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  • Title: Metabolism and nephrotoxicity of phenacetin and sulfanilamide.
    Author: Eyanagi R, Shigematsu H, Yoshida K, Yoshimura H.
    Journal: J Pharmacobiodyn; 1985 Feb; 8(2):95-105. PubMed ID: 4009405.
    Abstract:
    The mechanisms 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. On the other hand, the formation of p-aminophenol from phenacetin was also confirmed in rat kidney in vitro. These results suggested that 4-HABSA, N-hydroxyphenacetin and p-aminophenol formed in kidney play an important role in the renal damage produced by sulfanilamide and phenacetin.
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