Possible Interaction: Vitamin A and Fenretinide

“Although fenretinide is well tolerated even after prolonged use, it does lower plasma retinol levels and thus may affect night vision.”

“We speculate that fenretinide may interfere with the binding of vitamin A to opsin or with the transport of vitamin A.”

“Although retinol and 4HPR cross-competed for RBP binding, N-phenylretinamide, in which the 4-hydroxyl group is absent, and N-(4-methoxyphenyl)retinamide, a major cellular metabolite of 4HPR, in which the hydroxyl group is blocked, did not show affinity for the binding protein.”

“We show that retinol increases the affinity of RBP4 for TTR by a factor of 4 and determine the affinity constants of fenretinide and retinyl acetate.”

“ Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein.”

“Administration of the synthetic retinoid Fenretinide lowers circulating retinol and may thus affect night vision.”

“We have demonstrated, in animals and humans, that fenretinide induces a rapid reduction of retinol plasma concentration, that its blood levels remain constant during administration for as long as 5 years, and that the drug is able to accumulate in the human breast.”

“The tissue … of [3H]retinol increased by 50-130% following addition of 1.3 microM of all-trans-retinoic acid, 13-cis-retinoic acid, or …,4-didehydroretinoic acid (putative metabolites of retinol), and by 13-55% after addition of acitretin, arotenoid Ro 13-7410, or 4-(N-hydroxyphenyl)retinamide.”

“ 4HPR has recently been shown to induce a decrease of retinol and retinol binding protein (RBP) plasma levels in rats and humans (5, 6).”

“The ocular side effects of fenretinide , which resemble those of other synthetic retinoids (7), may be-due to the interference of these agents with vitamin A metabolism.”