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).
D000328:Adult; D000368:Aged; D000470:Alkaloids / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D004611:Ellipticines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding
D000470:Alkaloids; D000970:Antineoplastic Agents; D004611:Ellipticines; C027767:elliptinium