Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin.
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.
Smith
D B
DB
Margison
J M
JM
Lucas
S B
SB
Wilkinson
P M
PM
Howell
A
A
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
D015255:Idarubicin; D003630:Daunorubicin