Effect of Meals on the Kinetics of Etretinate

Eight healthy men received 100 mg oral doses of etretinate separated by two‐week washout periods in an open, randomized, crossover study. Etretinate was administered during a complete fast, with a standard high fat breakfast, a standard high carbohydrate breakfast, and 16 ounces of whole milk. Plasma samples were obtained at specific times over a 48‐hour period. Plasma concentrations of etretinate as well as two of its major metabolites were determined by a specific, reverse‐phase, high‐performance liquid chromatography method. Plasma concentrations of etretinate were greater when administered with a high fat meal and whole milk compared to ingestion with a high carbohydrate meal or during a complete fast. In contrast, there was no increase in the plasma concentrations of the active metabolites following any of the meals. These data indicate that chronic dosing of etretinate with milk or a high fat meal compared with fasting conditions will result in higher concentrations of etretinate, which may ultimately lead to higher metabolite concentrations.