Pharmacologic disposition of chemopreventive retinoids (review)

The disposition of natural and synthetic retinoids, some of which effectively prevent cancer in carcinogen-dosed animals, varies with the structure of the compound. Disappearance of retinoids from serum may be either linear or exponential, and there may be a prolonged terminal elimination phase. Metabolism of these compounds is extensive, with little or no absorbed retinoid being excreted unchanged. Compounds giving rise to retinol can be stored as retinyl esters in the liver. In contrast, retinoids with a terminal carboxyl group are not stored but are metabolized on the ring and/or on the sidechain prior to excretion, which occurs often after conjugation of the metabolites with glucuronic acid. Isomerization of the double bonds in the sidechain may also occur. The metabolites of natural retinoids do not appear to possess more biological activity than the parent compounds, leading to the conclusion that their metabolism is, in general, degradative.