Salicylamide pharmacokinetics in healthy males: dietary effect

The effect of diet on the absorption, metabolism, and elimination of salicylamide (SAM), in man was studied in five healthy male volunteers. In a three-way cross-over study, 300 mg SAM capsules were administered under fasting, carbohydrate, and lipid diet conditions. Total urinary salicylates, salicylamide glucuronide (SAMG), and salicylamide sulphate (SAMS) were determined at different time intervals. Diet was found to have no significant effect on the extent of SAM absorption or on its apparent elimination half-life. A significant increase (P less than 0.001) in the fraction excreted as SAMS in the lipid diet trial compared to the fasting or carbohydrate trials is observed. In the lipid diet trial, the ratio (R) of the cumulative urinary SAMS/SAMG was found to be 15-3 times the ratio obtained under fasting or carbohydrate diet conditions. The equilibrium solubilities of SAM under physiologic conditions in water (W), simulated intestinal fluid (M), and corn oil (O) were 4.08, and 4.81, and 12.5 mg ml-1, respectively. The equilibrium apparent distribution coefficients KO/W, KO/M, and KM/W were 3.1, 2.6 and 1.18, respectively. The increase in R is probably due to a decrease in free SAM concentration at the absorption site (intestinal mucosa) in the presence of lipids. A model for drug distribution in the gastrointestinal tract during lipid digestion is proposed and discussed.