Abstract
Addition of caffeine in vitro stimulated the oxidative metabolism of acetaminophen by rat liver microsomes, resulting in (a) increased formation of acetaminophen-glutathione (GSH) conjugates and (b) increased covalent binding of acetaminophen to microsomal protein. This metabolic enhancement by caffeine was most prominent using liver microsomes from phenobarbital (PB)-treated rats. Liver microsomes obtained from rats treated with ethanol-oxidized acetaminophen at much faster rates than microsomes from control, PB-treated or 3-methylcholanthrene (3-MC)-treated animals. The stimulatory effect of caffeine was, however, minimal in liver microsomes obtained from ethanol-treated rats.
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