Intestinal lymphatic transport of three retinoids in the rat after oral administration: Effect of lipophilicity and lipid vehicle

Abstract

The retinoids are highly lipophilic molecules and are known to be transported in the intestinal lymph after oral administration. Three retinoids, isotretinoin, etretinate and temarotene were used to study the effects of solubility and lipophilicity on lymphatic uptake in the rat after oral administration in each of three oily vehicles, cottonseed oil, Miglyol 812 and linoleic acid. Lipid solubility showed a general increase with increasing log P of the retinoid. The most lipophilic retinoid, temarotene, showed solubilities between 109.5 mg/ml (linoleic acid) and 170.6 mg/ml (Miglyol 812), whereas the least lipophilic retinoid, isotretinoin showed much lower solubilities between 5.1 (cottonseed oil) and 30.5 mg/ml (linoleic acid). Lymphatic uptake of temarotene was 4000-times and from etretinate 1000-times greater than that for isotretinoin after administration in linoleic acid. The lymphatic uptake of temarotene and etretinate from cottonseed oil were 27- and 26-times greater than that for isotretinoin and from Miglyol 812, 22- and 10-times greater than isotretinoin. These decreases in absorption via the lymphatic route reflect a decrease in log P value from temarotene (log P ~8.7) to etretinate (log P ~7.8) to isotretinoin (log P ~6.8). The rank order of increasing lymphatic uptake from each of the three oils shows an inverse relationship with solubility of the retinoid in each of the oils.