Plasma and human leukemic cell pharmacokinetics of oral and intravenous 4-demethoxydaunomycin.
On 3 consecutive days, 4-demethoxydaunomycin (D-DNM) was administered orally (30 mg/m2) as bolus injection and 4- or 24-hour infusion to seven patients with acute leukemia. Cellular (nucleated blood and bone marrow cells) and plasma drug concentrations were studied. After bolus injection, peak plasma D-DNM concentrations were about 50 mg/ml. D-DNM plasma t1/2s were 0.4 +/- 0.3 hours (T1/2 alpha) and 16.4 +/- 4.7 hours (T1/2 beta). D-DNM concentrations in nucleated blood and bone marrow cells were on the same order of magnitude and amounted to more than 400 times the plasma concentration, whereas 4-demethoxydaunomycinol (D-DNMol) concentrations were about 200 times higher. Cellular D-DNM concentrations were maximal at the end of intravenous dosing and at 2 to 4 hours after D-DNM ingestion. D-DNMol concentrations increased more slowly and accumulated on subsequent treatment days in cells and plasma; D-DNM and D-DNMol cellular t1/2 times were 42 and 72 hours, respectively. Antileukemic activity was observed.
Speth
P A
PA
van de Loo
F A
FA
Linssen
P C
PC
Wessels
H M
HM
Haanen
C
C
D000284:Administration, Oral; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D015255:Idarubicin; D007262:Infusions, Intravenous; D007700:Kinetics; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism
D015255:Idarubicin; D003630:Daunorubicin