Stability and compatibility of the investigational polymer-conjugated platinum anticancer agent AP 5280 in infusion systems and its hemolytic potential

AP 5280 is a novel polymer-conjugated platinum anticancer agent currently undergoing phase I clinical trials. It is pharmaceutically formulated as a lyophilized product containing 200 mg platinum per dosage unit. The aim of this study was to determine the reconstitution and dilution fluid of choice, and to investigate the stability and compatibility of AP 5280 in solution under different storage conditions and with several container materials. Furthermore, the hemolytic potential of AP 5280 infusion solution was investigated in vitro. AP 5280 slowly released small platinum species in all solutions, although this release was enhanced in normal saline. Accordingly, 5% dextrose in water (D5W) was selected for reconstitution and dilution of AP 5280. Container material [glass or polyvinylchlorlde (PVC)] did not influence the stability of AP 5280 in solution. Storage at refrigerated temperature (2-8 degreesC) marginally decreased the release rate of liberated platinum. The infusion solutions are compatible with the PVC infusion system and do not cause hemolysis in vitro. In conclusion, AP 5280 lyophilized product should be reconstituted and diluted to infusion concentration with D5W, and administered within 8 h after preparation to ensure that less than 1.0% of the total platinum concentration is present as liberated platinum. [(C) 2002 Lippincott Williams Wilkins.].