CLINICAL PHARMACOKINETICS OF AMONAFIDE (NSC-308847) IN 62 PATIENTS

Amonafide (A) demonstrates dose-related increases in area under the cu rve (AUC) and Cmax values. Total body clearance for A (ranging from 44 .2 to 53.8 L/hr/m(2)) is relatively constant within the dosing range o f this study. The dose-related increase of AUC was also observed for t he two identified metabolites, acetylamonafide (AA) and noramonafide ( NA). A and NA plasma data could be described by a four-compartmental m odel (two compartments for A, one compartment each for NA and AA). The fitting for NA was poor owing to its low plasma concentration. The te rminal half-lives for A, NA, and AA were in the range of 3-5 hr. No cu mulative accumulation of parent compound or metabolites was detected a fter daily administration. The concentrations of A, NA, and AA 24 hr a fter dosing were either below or very close to the quantitative limits of the assay. Polymorphic disposition of A was confirmed by a frequen cy distribution of AUC value versus dose plot.