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Plasma and human leukemic cell pharmacokinetics of oral and intravenous 4‐demethoxydaunomycin
Author(s) -
Speth Paul A J,
Loo Fons A J,
Linssen Peter C M,
Wessels Hans M C,
Haanen Clemens
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.239
Subject(s) - pharmacokinetics , intravenous bolus , bolus (digestion) , bone marrow , plasma concentration , pharmacology , ingestion , chemistry , dosing , medicine , endocrinology
On 3 consecutive days, 4‐demethoxydaunomycin (D‐DNM) was administered orally (30 mg/m 2 ) 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 t ½ s were 0.4 ± 0.3 hours (T ½α ) and 16.4 ± 4.7 hours (T ½β ). 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 t ½ times were 42 and 72 hours, respectively. Antileukemic activity was observed. Clinical Pharmacology and Therapeutics (1986) 40 , 643–649; doi: 10.1038/clpt.1986.239