Comparative bioavailability: influence of various diets on the bioavailability of indomethacin

After oral application of 100 mg indomethacin to eight healthy male volunteers, the concentrations in plasma and their time course were determined when the drug was given to fasting individuals or after a high-protein, a high-lipid or a high-carbohydrate meal. The study was designed as a fourfold-crossover experiement with intermissions of at least one week between applications. Indomethacin in plasma was determined by fluorimetry after a double extraction procedure. Indomethacin plasma concentrations and the truncated areas under the curves (AUC) were evaluated. Administration to fasting subjects provides higher plasma levels and a smaller tmax value than after either one of the three diets. Also the absorption rate was higher in fasting individuals. However, the absorbed amount of indomethacin after 24 hr was practically equal in all four groups. Attempts to distinguish between the effects of the various diets revealed significant differences in the time period necessary to reach the peak values. After high-protein and high-lipid diets they were reached in the 90 min sample while after high-carbohydrate 120 min were required. These values are significantly different from fasting controls (45 min) and from each other. There is no great influence of food on the other aspect of bioavailability, amount of unchanged drug reaching the systemic circulation.