title: Compatibility and stability of the novel anti-cancer agent C1311 in infusion devices and its in vitro biocompatibility.
abstract: C1311 is the lead compound from the imidazoacridinones, a novel group of rationally designed anti-cancer agents. The compound is pharmaceutically formulated as a lyophilized product containing 100 mg C1311 (anhydrous free base) per dosage unit and requires reconstitution before intravenous administration. The aim of this study was to determine the stability of C1311 in the reconstituted solution and infusion solution and its compatibility with infusion devices. Moreover, the buffer capacity and haemolytic potential of C1311 infusion solutions, which exhibit a relatively low pH of 2-3, were evaluated in vitro. C1311 was shown to be stable in the reconstituted solution for at least 48 h and for at least 96 h after subsequent dilution in 0.9% sodium chloride and 5% dextrose. In vitro infusion simulation studies showed C1311 infusion solutions to be compatible with a low-density polyethylene administration set. Furthermore, the buffer capacity and haemolysis studies showed no indications for haemolysis or potential for vascular irritation upon continuous infusion of C1311. In conclusion, C1311 lyophilized product is adequately stable and compatible after reconstitution and in infusion fluids to be used in the clinic and is not expected to cause formulation-associated side effects in the intended administration schedule in the forthcoming Phase I clinical study.
authors.affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apmbk@slz.nl
authors.forename: Monique W J
authors.initials: MW
authors.lastname: den Brok
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Nuijen
authors.forename: Remko
authors.initials: R
authors.lastname: Harms
authors.forename: Josie N
authors.initials: JN
authors.lastname: Buluran
authors.forename: Michael D
authors.initials: MD
authors.lastname: Harvey
authors.forename: Charles K
authors.initials: CK
authors.lastname: Grieshaber
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000609:Aminoacridines / Q000009:adverse effects / Q000032:analysis*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000032:analysis*; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004344:Drug Incompatibility; D004355:Drug Stability; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007262:Infusions, Intravenous
chemical_list: D000609:Aminoacridines; D000970:Antineoplastic Agents; D002021:Buffers; C098965:C 1311