Altered metabolism of all-trans-retinoic acid in liposome-encapsulated form

Treatment with all-trans-retinoic acid (ATRA) induces complete remission in many acute promyelocytic leukemia patients. However, plasma drug levels pr ogressively decrease following prolonged treatment with oral ATRA. This dec rease is due, at least in pan, to the induced cytochrome P-450-dependent me tabolism of ATRA. To investigate if incorporation of ATRA in liposomes coul d alter its metabolism, we compared the cellular metabolism of liposomal-AT RA (L-ATRA) with free drug. Microsomes isolated from the rat liver metaboli zed L-ATRA to a significantly lower extent than they did free-ATRA. Similar ly, in F9 cells, L-ATRA was metabolized at a slower rate than the free drug . These results suggest that L-ATRA may have important clinical implication s in terms of slowing down the rate of ATRA metabolism and producing long-t erm remission in APL patients. (C) 1998 Elsevier Science ireland Ltd. All r ights reserved.