title: Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin.
abstract: The clinical pharmacology of 4-demethoxydaunorubicin (4-DMDNR) was studied in 28 patients with advanced breast cancer, using a sensitive reverse-phase HPLC technique. All patients had normal renal and hepatic function. The serum levels of 4-DMDNR after a single i.v. bolus injection followed a triple exponential decay curve (T 1/2 alpha = 9.6 min, T 1/2 beta = 3.2 h and T 1/2 gamma = 34.7 h) and conformed to a three-compartment model. Comparison of the area under the curve (AUC) and urinary excretion for the oral and i.v. routes suggests an oral bioavailability of approximately 24%. In patients treated with a schedule of weekly oral administration for periods of up to 12 months there was no significant alteration in either AUC or elimination half-life for the parent drug or its principal metabolite 13-OH4DMDNR. Moreover, there was no evidence of accumulation of the metabolite although measurable amounts were present 7 days after administration of 4-DMDNR.
authors.forename: D B
authors.initials: DB
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Margison
authors.forename: S B
authors.initials: SB
authors.lastname: Lucas
authors.forename: P M
authors.initials: PM
authors.lastname: Wilkinson
authors.forename: A
authors.initials: A
authors.lastname: Howell
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy; D003630:Daunorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015255:Idarubicin; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate
chemical_list: D015255:Idarubicin; D003630:Daunorubicin