Compatibility and stability of Imexon in infusion devices and its in vitro biocompatibility.

Abstract:

:Imexon is an investigational anti-cancer agent, pharmaceutically formulated as a lyophilized solid for i.v. infusion requiring reconstitution and subsequent dilution in infusion fluid before infusion. Imexon contains a highly reactive aziridine ring in its structure, which limits its stability in aqueous solutions. In the present study, several in vitro studies were conducted to determine the administration parameters for use in the forthcoming phase I clinical trial. The stability of Imexon in the reconstituted solution and infusion solutions was investigated, including its tendency to degrade to its main degradation product BM41.209, and to its hydroxy and chloride adducts. The compatibility of the infusion solution with glass, low-density polyethylene and freeflex polyolefin containers, and its potency to cause vascular irritation and hemolysis upon i.v. infusion were investigated. Imexon was found to be stable for 8 h in the reconstituted product and for 2 h after dilution to infusion solution concentrations in normal saline. The infusion solution was compatible with the freeflex polyolefin container and polyvinylchloride infusion lining, showing no sorption of Imexon during a 15-min infusion duration and no release of the plasticizer diethylhexyl phthalate. Furthermore, Imexon infusion solution showed no indication for vascular irritation or hemolysis upon i.v. infusion, as measured with a static in vitro model with incubation with whole blood. In conclusion, Imexon should be administered using a freeflex polyolefin infusion container within 2 h after preparation and a 15-min infusion duration. The results obtained with an in vitro model show that no vascular irritation or hemolysis is expected upon i.v. infusion.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

den Brok MW,Nuijen B,Challa EE,Lutz C,Opitz HG,Beijnen JH

doi

10.1097/01.cad.0000172833.70444.ba

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

727-32

issue

7

eissn

0959-4973

issn

1473-5741

pii

00001813-200508000-00005

journal_volume

16

pub_type

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