Pharmaceutical development of the novel metal-based anticancer agents NAMI-A and AP 5280

Abstract

The pharmaceutical development of the two novel metal-based anticancer agents NAMI-A and AP 5280 is described in this thesis, starting with the development of analytical methods for the quality control of drug substance and final product, via the formulation process leading to a stable, intravenous administration form, and ending with the stability and compatibility studies of the infusion solutions. This research could also serve as the basis for the pharmaceutical development of other novel, metal-based anticancer agents. Because many metals exchange ligands easily, the compounds will usually not be stable in solution, necessitating preparation of a lyophilized product. NAMI-A and AP 5280 are examples of this. The experiments described in this thesis enabled the clinical evaluation of NAMI-A and AP 5280. At this time, 23 patients have been treated with NAMI-A and 30 with AP 5280 in the clinical Phase I study. Subsequent Phase II studies will provide insight into the clinical efficacy of these agents