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 progressively decrease following prolonged treatment with oral ATRA. This decrease is due, at least in part, to the induced cytochrome P-450-dependent metabolism of ATRA. To investigate if incorporation of ATRA in liposomes could alter its metabolism, we compared the cellular metabolism of liposomal-ATRA (L-ATRA) with free drug. Microsomes isolated from the rat liver metabolized L-ATRA to a significantly lower extent than they did free-ATRA. Similarly, 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 implications in terms of slowing down the rate of ATRA metabolism and producing long-term remission in APL patients.