Identification of 4-oxo-13-cis-retinoic acid as the major metabolite of 13-cis-retinoic acid in human blood.
The metabolites of 13-cis-retinoic acid (Accutane) were investigated in blood samples from human volunteers on chronic treatment for dermatological disorders. The major metabolite was isolated by reverse-phase high-pressure liquid chromatography and identified as 4-oxo-13-cis-retinoic acid by comparison of its mass and NMR spectra to the spectra of the reference compound. 4-Oxo-all-trans-retinoic acid was also identified, but the extent to which this compound was a metabolite of 13-cis-retinoic acid or an artifactual isomerization product of the major metabolite is unknown. Chromatographic data suggested that small amounts of 13-cis-retinoic acid, 4-hydroxy-13-cis-retinoic acid, and dioxygenated metabolites of 13-cis-retinoic acid may also be present in the blood. This study indicates that a major metabolic pathway of 13-cis-retinoic acid in humans is oxidation at C4 of the cyclohexenyl group.
D006801:Humans; D007536:Isomerism; D015474:Isotretinoin; D010084:Oxidation-Reduction; D012871:Skin Diseases / Q000188:drug therapy; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use
C002202:4-oxoretinoic acid; D014212:Tretinoin; C019429:4-hydroxyretinoic acid; D015474:Isotretinoin