Effects of meals and meal composition on the bioavailability of fenretinide.
The effects of meals and meal composition on the bioavailability of fenretinide, N-(4-hydroxyphenyl) retinamide, a synthetic retinoid undergoing clinical trials, were examined in two separate studies using an open, randomized, crossover design. In the first study, 13 healthy male volunteers received 300-mg doses of fenretinide (1) while fasting and (2) after a high-fat breakfast. In a subsequent study, 15 subjects received 300 mg fenretinide after each of three different test meals (high-fat, high-protein, and high-carbohydrate) separated by a 1-week washout period. Plasma specimens obtained over a 72-hour period after each treatment were assayed by high-pressure liquid chromatography to characterize the effects of a meal and meal composition on the bioavailability of fenretinide. Results from the initial study demonstrated a significant increase in the bioavailability of fenretinide after a high-fat meal. In the follow-up study, the bioavailability of fenretinide, as assessed by total area under the plasma concentration curve, was three times greater after the high-fat meal than after the high-carbohydrate meal. This supported the findings of the first study. Although to a lesser extent, the high-protein meal also produced a greater area under the curve than the high-carbohydrate meal. These combined findings demonstrate that the bioavailability of fenretinide is markedly influenced not only by administration with meals but also by the specific composition of such meals.
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R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477-0776.
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Stellar
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Nayak
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D000328:Adult; D001682:Biological Availability; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000378:metabolism; D017313:Fenretinide / Q000097:blood / Q000493:pharmacokinetics*; D005502:Food; D006801:Humans; D008297:Male; D008875:Middle Aged
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D017313:Fenretinide