ANTI-TUMOR ACTIVITY OF PROLONGED-RELEASE DERIVATIVE OF CYTOSINE-ARABINOSIDE, CYTOSINE ARABINOSIDE-AGAROSE CONJUGATE

Abstract

A prolonged-release derivative of cytosine arabinoside (Ara-C), cytosine arabinoside-agarose bead conjugate (Ara-C-AB), was synthesized and its pharmaceutical and pharmacological characteristics were examined. Ara-C was released successively for a considerably long period from Ara-C-AB in vitro. Following i.p. injection of 3H-Ara-C-AB, radioactivity could be detected in plasma and urine of BDF1 mouse for 4 days, while 3H-Ara-C administered as a free form was excreted completely in the first 24 h. Increase in lifespan of L1210 leukemia-bearing mice was demonstrated after i.p. injection of Ara-C-AB with both the dosage schedules of 3 days before and 1 day after inoculation of L1210 cells at the dose of 30 mg equivalent ARa-C/kg.