Influence of various diets on the bioavailability of isoniazid

Abstract

The influence of various test meals on the bioavailability of isoniazid (INH) was examined by a cross-over study in 10 healthy volunteers of which six were slow and four rapid acetylators. INH was administered as a single dose of 300 mg in the fasting state and together with a low-fat milk, a high-fat/protein or a high carbohydrate meal (300 kcal). Serum concentrations of INH and acetyl-INH (Ac-INH) were determined spectrophotometrically and by a high-performance liquid chromatographical method, respectively. Peak serum concentrations of INH were achieved earlier and were higher when the drug was taken without food both in the slow and rapid acetylators. Also the areas under drug concentration-time curves were significantly larger after fasting than after any test meal; the difference was most prominent after the carbohydrate meal possibly because INH can form unabsorbable condensation products with various sugars. Elimination half-lives of INH were significantly longer in the slow acetylators than in the rapid. Serum acetyl-INH levels were always about twice as high in the rapid acetylators than in the slow. The effect of food on acetyl-INH levels was similar. The rate and extent of absorption of INH from one 300mg and six 50mg tablets were not significantly different.