Pharmacokinetics studies on the interaction between acetaminophen and salicylamide in rats

Acetaminophen and salicylamide are well known to have first-pass effects after their oral administration. The present investigation was conducted to study the effect of salicylamide on the first-pass effect of acetaminophen after oral or intraduodenal administration. Male Wistar rats were chosen as the experimental animals for this study. The plasma concentrations of acetaminophen and its two major metabolites, the glucuronide (acetaminophen glucuronide) and sulphate (acetaminophen sulphate) conjugates, were measured, using HPLC after enzymatic hydrolysis, in order to calculate the first-pass effect. The results showed a decrease in the first-pass effect of acetaminophen when it was administered with salicylamide. This effect was clearly observed via the marked increase in the area under the plasma concentration/time curve of the unchanged acetaminophen. On the other hand, the concentrations of acetaminophen sulphate through the absorption phase were significantly decreased in comparison with that of the control. The plasma concentration data after the intraduodenal co-administration of salicylamide (50 and 100 μmol/kg) with acetaminophen (100 μmol/kg) were applied to the expected pharmacokinetic model containing the absorption phase. The computer fitting of these data showed a decrease in the first-pass parameters emphasizing the pronounced effect of salicylamide in decreasing the intestinal anal or the hepatic first-pass effect of acetaminophen, and the increase in the absorption rate constant k(a), as well as the Michaelis-Menten constant, K(m), for sulphate conjugation.