Blood level studies of all-trans- and 13-cis-retinoic acids in rats using different formulations

Studies to determine the bioavailability of all-trans-retinoic acid from a microencapsulated product were carried out using rats as test animals. The microcapsules were tableted in rat food and individual rats given a tablet containing the equivalent of 10 mg of all-trans-retinoic acid. Comparisons were made with bioavailability data obtained after intravenous and oral administrations of a solution and a suspension. The elimination of all-trans-retinoic acid following intravenous administration of 1- to 5-mg doses occurred by dose-dependent kinetics. The half-lives for the terminal linear portion of the elimination phase after the plateau level were 0.78, 0.74, and 0.93 hr for the 1-, 2.5-, and 5-mg doses, respectively. Based on the doses administered and the relative area under the serum level curves, the all-trans-retinoic acid microcapsules were found to be approximately 34% as bioavailable as the solution dosage form and the microfine suspension 93% as bioavailable. The bioavailability of all-trans-retinoic acid in oral solution was approximately 40% of the intravenous dose. For comparison, rats were also dosed intravenously with 13-cis-retinoic acid, and this compound was found not to follow dose-dependent kinetics at similar dosage levels used for all-trans-retinoic acid.