PERCUTANEOUS-ABSORPTION, EXCRETION AND METABOLISM OF ALL-TRANS-RETINOYL BETA-GLUCURONIDE AND OF ALL-TRANS-RETINOIC ACID IN THE RAT

The purpose of these studies was to compare directly the percutaneous absorption, excretion and metabolism of all-trans-retinoyl beta-glucur onide (RAG), a nontoxic retinoid, with all-trans-retinoic acid (RA) in the rat. Previously, it was demonstrated that topical treatment of hu man acne with either RAG or RA in cream resulted in a significant redu ction of lesions. Whereas 0.1% RA showed adverse effects, concentratio ns of RAG up to 2.4% did not cause any adverse reactions. In the prese nt studies, radiolabeled RAG or RA, dispersed in a water-based cream, was applied to the shaved dorsal skin of vitamin A-sufficient rats. Bo th RAG and RA were absorbed from the skin in a similar way. In both ca ses, radioactivity peaked in the plasma within 2-4 h and within the li ver at 4-12 h. During a 7-day period, the overall excretion of radioac tivity derived from RA and RAG in the feces and urine were similar, e. g. 17 and 12%, respectively. It is concluded that: (1) the transport, metabolism and excretion of topically applied radioactive RA and RAG a re similar, although not identical, in the rat and (2) the toxic skin manifestations induced by RA but not by RAG cannot be attributed to ma jor differences in their overall absorption, metabolism and excretion.