DRUG METABOLISM AND DIsr’osmoN Copyright 10 1996 by The American Society for Pharmacology and Experimental Therapeutics Short Communication Excretion of Oral 9-Cis-Retinoic Acid in the Rat

We have studied excretion of oral 9-cis-retinoic acid in urine and feces in vigil rats and in bile in anesthetized rats. A proportion of 53 ± 13 % of the dose of 9-cis-retinoic acid administered was elimi-nated through the feces in 72 hr, and the urinary excretion was negligible. The prevalent form of elimination In feces and urine was the unchanged compound. Low billary excretion was, for the most part, composed of metabolftes. Retinoids are a large group of compounds that are structurally related to vitamin A. The pleiotropic biological effects of retinoids are thought to be mediated through two families of nuclear receptors: RXRs ’ and RARs (1). 9-Cis-RA has been found to bind and activate both RARs and RXRs (1, 2). All-trans-RA and 13-cis-RA are used as therapeutic agents in dermatology, particularly in the treatment of severe cystic acne (3). 9-Cis-RA, obtained by isomerization of all-trans-RA (4), has attracted much attention as a potent effector in oncology (5). Only limited information is available on the elimination of 9-cis-RA. Studies performed with mice (6) have demonstrated the rapid elimination of 9-cis-RA. Work on the pharmacokinetics of 9-cis-RA after intravenous administration to rhesus monkeys has revealed rapid elimination (7). In the present work, the excretion of the 9-cis-RA in urine and feces in vigil rats and bile in the same anesthetized rats was investigated. Laboratory Precautions. All laboratory manipulations involving the retinoids were performed in a dark room under dim yellow light to prevent photoisomerization. Chemicals. The retinoids, 9-cis-RA, all-trans-RA, 13-cis-RA, 9-cis-4-oxo-RA, all-trans-4-oxo-RA, and 13-cis-4-oxo-RA wer