Abstract
Following oral administration of doses of 10 mg/kg, the concentrations of all-trans-retinoic acid (RA), N-(2-hydroxyethyl)retinamide (N-HOERA), and 13-cis-retinoic acid (13-cis-RA) were measured in serum and tissues of mice with and without pretreatment with phenobarbital (PB), 3-methylcholanthrene (3MC), or the respective retinoid. For RA, the areas under the concentration-time curves (AUC values) for serum and tissues, relative to controls, were reduced, on the average, by 54 or 37% on pretreatment with RA or PB, respectively. Pretreatment with 3MC did not affect disposition of RA. The AUC values for N-HOERA were reduced, on the average, by 39 or 30% following pretreatment with PB or 3MC, respectively, but only 13% by the retinoid. For 13-cis-RA, the AUC values were reduced, on the average, by 56 or 37% following pretreatment with PB or 3MC, respectively; pretreatment with the retinoid had no appreciable effect. Thus, the disposition of orally administered retinoids appears to be affected by several inducible metabolic processes. Furthermore, comparison of data on the tissue distribution of retinoids with in vivo results demonstrates a general correlation between distribution and anticarcinogenic activity.
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