Pharmacokinetics of 2-methyl-9-hydroxyellipticinium Acetate (NSC-264137) in Cancer Patients (phase I Study)

In 12 cancer patients we studied the pharmacokinetics of a new antitumor compound, elliptinium, which is a quaternary ammonium derivative of ellipticine, after i.v. infusion. The main parameters were calculated by means of the ADAPT program based upon plasma concentrations and urinary elimination determined by a high performance liquid chromatographic assay and fluorescence detection. The mean apparent volume of distribution for the central compartment, V1, is 2.8 l, the total plasma clearance is 971 ml/min, with a renal clearance of 127 ml/min. The mean elimination half-life, t1/2, z, is 23.7 hr, but shows a large interindividual variation. Urinary elimination is quite low (16%), with the main part (12%) excreted in the first 24 hr. In vitro plasma protein binding (78%) was found to be independent of the concentration (0.1-5.0 micrograms/ml).