Disposition of all-trans- and 13-cis-retinoic acids and n-hydroxyethylretinamide in mice after intravenous administration.

The disposition of 13-cis- and all- trans-retinoic acids and N-hydroxyethylretinamide has been studied in mice after an intravenous dose of 10 mg/kg. As determined by high-ressure liquid chromatography, serum levels of 13-cis-retinoic acid, in a distribution phase, decreased rapidly over a 30-min period. This was followed by an apparently exponential phase of elimination. N-Hydroxyethylretinamide had a distribution phase lasting for 1 hr followed by an exponential phase. All-trans-retinoic acid had a similar distribution phase, but this was followed by a nonexponential phase. Tissue levels of 13-cis-retinoic acid, although generally not as high as those in serum, decreased in a manner similar to that for serum. Levels of all-trans-retinoic acid in liver, kidney, lung, brain, and small intestine were generally higher than those of serum throughout the period of observation. At 8 hr after injection of the mice, relatively high levels of all-trans-retinoic acid remained in the brains, and detectable levels of 13-cis-retinoic acid persisted in the lungs. N-Hydroxyethylretinamide also persisted in tissues for long periods of time, with tissue levels generally higher than those in serum. At 18 hr after injection of mice, relatively high levels of this compound were found in the liver, kidneys, and testes.