FORMATION, METABOLISM, AND EXCRETION OF CONJUGATES OF PARACETAMOL

This chapter discusses the formation, metabolism, and excretion of paracetamol in freshly isolated cells from rat liver, kidney, and small intestine, and in the isolated perfused liver and the closed intestinal segment. Paracetamol is subject to oxidative and conjugative metabolism in several tissues resulting in formation of a variety of products. It is metabolized by direct conjugation with sulfate and glucuronic acid. Paracetamol may also undergo a cytochrome P-450 dependent activation to form a reactive species that conjugates with reduced glutathione forming paracetamol-S-glutathione. The glutathione conjugate may be further metabolized by γ-glutamyltranspeptidase. Initially, the γ-glutamyl group is removed followed by peptidase-catalyzed hydrolysis of the cysteinyl glycine conjugate. The remaining cysteine conjugate may, then, undergo N-acetylation to form the N-acetylcysteine conjugate