The Rate of Aniline Metabolismin vivoin Rats Exposed to Aniline and Drugs

Abstract

1. The rates of aniline metabolism have been studied in vitro using rat liver homogenates, and in vivo by determination of the unchanged aniline remaining in the cadaver. 2. Metabolism of aniline in vivo is stimulated by phenobarbital and 3,4-benzpyrene, and inhibited by SKF 525-A. 3. Cyclobarbital and phenacetin stimulate aniline metabolism both in vitro and in vivo. 4. Pre-treatment with aniline impaired the metabolism of aniline in vivo but increased the in vitro metabolism to p-aminophenol. Pre-treatment of rats with phenobarbital and aniline did not accelerate metabolism of aniline in vivo but the stimulating effect of phenobarbital on protein synthesis in microsomes was maintained. In contrast, pre-treatment with 3,4-benzpyrene and aniline stimulated metabolism of aniline in vivo. The possible mechanism of changes in aniline metabolism due to previous exposure to aniline is discussed.

Structural Features of Cytochromes P450 and Ligands that Affect Drug Metabolism as Revealed by X-Ray Crystallography and NMR

“…Another substrate, aniline, is metabolized by CYP2B1 and CYP1A1 via two competing reactions: N -hydroxylation and p -hydroxylation [93–95]. An NMR study was performed with structural isomers of methylfluoroaniline and these P450s to study regioselectivity and the mechanism of aniline metabolism [96].…”