REPEATED TOPICAL ADMINISTRATION OF ALL-TRANS-RETINOIC ACID AND PLASMA-LEVELS OF RETINOIC ACIDS IN HUMANS

Background: Vitamin A ingestion raises plasma levels of several potent ially teratogenic retinoic acids (RAs) with all-trans and 13-cis confi guration, but definitive data concerning the consequences of topical a dministration of all-trans-RA are lacking. Objective: The study object ive was to investigate the potential for inducing systemic activity af ter topical administration of 0.025% all-trans-RA by measuring plasma retinoid levels. Methods: Plasma levels of all-trans-RA, 13-cis-RA, an d 4-oxo-13-cis-RA were measured in four healthy subjects before, durin g, and after 14 daily topical applications of all-trans-RA. Results: T opical administration of all-trans-RA did not significantly increase p lasma levels of all-trans-RA, 13-cis-RA, and 4-oxo-13-cis-RA. Signific ant decreases in levels of these RAs observed during the night may ref lect diurnal variations of retinoid metabolism or lowered absorption o f dietary vitamin A. Conclusion: Diurnal and nutritional factors influ ence plasma levels of endogenous retinoids to a greater extent than to pical administration of all-trans-RA at doses used for acne therapy, w hich on the basis of these results appears unlikely to induce systemic effects.