Kinetics and sensitivity of daunorubicin in patients with acute leukemia

Michael W. DeGregorio, Walter M. Holleran, Bruce A. Macher, Charles A. Linker, Jordan R. Wilbur

Research output: Contribution to journalArticle

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Abstract

Leukemia cells isolated from eight patients with acute leukemia before treatment were examined for in vitro uptake of daunorubicin (DNR) and inhibition of DNA synthesis. In addition, plasma and cellular levels of DNR and daunorubicinol (DOL) were examined in six of the eight patients. Inhibition of DNA synthesis was determined with a 3H-thymidine incorporation assay. In vitro cellular 14C-DNR was quantified by means of liquid scintillation spectrometry, whereas in vivo DNR and DOL concentrations were determined by high-performance liquid chromatography. In vitro intracellular plateau concentrations of DNR were achieved within 1-2 h after continuous exposure to 0.01, 0.1, and 1.0 ug/ml in the majority of cases. Based on our in vitro studies, a dose-response curve was found between increasing intracellular DNR and incorporation of 3H-thymidine. Peak intracellular levels of DNR after treatment occurred immediately after administration of the drug, whereas intracellular DOL levels accumulated over several hours. Plasma concentrations of DNR and DOL were not useful in estimating target tissue concentrations or inhibition of 3H-thymidine incorporation. Extrapolation of in vivo cellular DNR concentrations to the in vitro dose-response curve allows an estimate of DNR sensitivity.

Original languageEnglish (US)
Pages (from-to)230-234
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume13
Issue number3
DOIs
StatePublished - Oct 1984

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Daunorubicin
Leukemia
Kinetics
Thymidine
Plasmas
DNA
High performance liquid chromatography
Scintillation
Extrapolation
Spectrum Analysis
Spectrometry
Assays
High Pressure Liquid Chromatography
In Vitro Techniques
Tissue
daunorubicinol

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

DeGregorio, M. W., Holleran, W. M., Macher, B. A., Linker, C. A., & Wilbur, J. R. (1984). Kinetics and sensitivity of daunorubicin in patients with acute leukemia. Cancer Chemotherapy and Pharmacology, 13(3), 230-234. https://doi.org/10.1007/BF00269036

Kinetics and sensitivity of daunorubicin in patients with acute leukemia. / DeGregorio, Michael W.; Holleran, Walter M.; Macher, Bruce A.; Linker, Charles A.; Wilbur, Jordan R.

In: Cancer Chemotherapy and Pharmacology, Vol. 13, No. 3, 10.1984, p. 230-234.

Research output: Contribution to journalArticle

DeGregorio, MW, Holleran, WM, Macher, BA, Linker, CA & Wilbur, JR 1984, 'Kinetics and sensitivity of daunorubicin in patients with acute leukemia', Cancer Chemotherapy and Pharmacology, vol. 13, no. 3, pp. 230-234. https://doi.org/10.1007/BF00269036
DeGregorio, Michael W. ; Holleran, Walter M. ; Macher, Bruce A. ; Linker, Charles A. ; Wilbur, Jordan R. / Kinetics and sensitivity of daunorubicin in patients with acute leukemia. In: Cancer Chemotherapy and Pharmacology. 1984 ; Vol. 13, No. 3. pp. 230-234.
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