DIFFERENCES IN THE LIPOPROTEIN DISTRIBUTION OF FREE AND LIPOSOME-ASSOCIATED ALL-TRANS-RETINOIC ACID IN HUMAN, DOG, AND RAT PLASMA ARE DUE TO VARIATIONS IN LIPOPROTEIN LIPID AND PROTEIN-CONTENT

The objective of the proposed study was to determine the distribution in plasma lipoprotein of free all-trans retinoic acid (ATRA) and lipos omal ATRA (Atragen; composed of dimyristoyl phosphatidylcholine and so ybean oil) following incubation in human, rat, and dog plasma. When AT RA and Atragen at concentrations of 1, 5, 10, and 25 mu g/ml mere incu bated in human and rat plasma for 5, 60, and 180 min, the majority of the tretinoin was recovered in the lipoprotein-deficient plasma fracti on. However, when ATRA and Atragen mere incubated in dog plasma, the m ajority of the tretinoin (>40%) was recovered in the high-density lipo protein (HDL) fraction. No differences in the plasma distribution betw een ATRA and Atragen mere found. These data suggest that a significant percentage of tretinoin associates with plasma lipoproteins (primaril y the HDL fraction) upon incubation in human, dog, and rat plasma. Dif ferences between the lipoprotein lipid and protein profiles in human p lasma and in dog and rat plasma influenced the plasma distribution of ATRA and Atragen, Differences in lipoprotein distribution between ATRA and Atragen were not observed, suggesting that the drug's distributio n in plasma is not influenced by its incorporation into these liposome s.