IN VITRO METABOLISM OF THREE MAJOR ISOMERS OF RETINOIC ACID IN RATS Intersex and Interstrain Comparison

Cytochrome P450 expression in liver is influenced by several fac-tors, including sex and strain. Whereas little is known about their metabolic capabilities, Hairless rats are widely used for the studies of topical agents. We compared Sprague-Dawley and Hairless rat metabolic behavior to validate the use of Hairless rats in pharma-cokinetic and metabolic studies of topically applied drugs. Liver microsomes of male and female rats of both strains were used to investigate the in vitro metabolism of three retinoic acid (RA) iso-mers: all-trans-RA, 13-cis-RA, and 9-cis-RA. In all cases, a major isomerization of the tested isomer in the two others was observed. This process was independent of the presence of NADPH, but depended on the presence of microsomal proteins. In addition, we observed, to a lesser extent, the formation of 4-oxo metabolites (4-oxo-all-trans-RA, 4-oxo-13-cis-RA, and 4-oxo-9-cis-RA), with the rate of formation of each of these compounds varying with th