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Enhanced phenacetin metabolism in human subjects fed charcoal‐broiled beef

There were marked individual differences in the plasma levels of phenacetin after oral administration of a 900‐mg dose to 9 normal volunteers eating their customary home diet. Feeding a diet that contained charcoal‐broiled beeffor 4 days prior to the administration of phenacetin markedly decreased the plasma levels of this drug without appreciably influencing the plasma concentrations of phenacetin's metabolite, N‐acetyl‐p‐aminophenol (APAP), or the plasma half‐life of phenacetin. The average peak concentration of phenacetin in plasma, after a 900‐mg oral dose, fell from 1,628 ng/ml, when the subjects were fed a control diet for 7 days, to 352 ng/ml after they were fed the same diet which contained charcoal‐broiled beeffor 4 days. The average peak concentration of phenacetin rose to 1,885 ng Iml after the subjects were subsequently fed the control diet for 7 days. The ratios of the average concentrations of APAP in plasma to those of phenacetin markedly increased after the charcoal‐broiled beef diet. The results suggest that a diet containing charcoal‐broiled beef enhances the metabolism of phenacetin in the gastrointestinal tract and/or during its first pass through the liver. This effect greatly decreases the bioavailability of phenacetin.