Possible Interaction: Caffeine and Phenacetin

“Three monooxygenase activities (methoxyresorufin O-demethylase, phenacetin O-deethylase and acetanilide 4-hydroxylase) correlated significantly with the rate of metabolism of caffeine.”

“Other putative human CYP1A xenobiotic substrates and inhibitors, including caffeine , 5- and 8-methoxypsoralen, nifedipine, paraxanthine, propranolol and theophylline similarly inhibited CYP1A1- and 1A2-catalyzed phenacetin O-deethylation and the high-affinity human liver phenacetin O-deethylase.”

“However, there was a significant enhancement of a multifocal tumor development (… rats with more than 1 tumor in the bladder), when additionally phenacetin was fed alone (44% of the … animals) or in combination with caffeine (47%) compared with the control rats treated … BBN alone which showed only solitary tumors.”

“Forty percent of the rats treated with caffeine only or with caffeine and phenacetin in combination were found to have periarteritis nodosa-like lesions in the mesenteric vessels.”

“The antipyretic activity of phenacetin was higher but that of caffeine was lower than that of aspirin.”

“Addition of caffeine to the combination of aspirin and phenacetin caused a significant increase in erosions, but when given with aspirin and paracetamol no erosions occurred.”

“In contrast, caffeine had only a minor influence on the absorption and metabolism of phenacetin.”

“ Phenacetin initially retarded the absorption of caffeine when coadministered by gavage but not when caffeine was given intraperitoneally and phenacetin orally.”

“The interactive effects of caffeine and phenacetin on the locomotor activity of the DA rat involved changes in absorption and metabolism as well as effects possibly exerted at the cns level.”

“Urinary excretion patterns, suggested a blockade of the N‐demethylation of caffeine by phenacetin.”