Clinical pharmacology of 4-demethoxydaunorubicin (DMDR)

Katherine Lu, Niramol Savaraj, John Kavanagh, Lynn G Feun, Michael Burgess, Gerald P. Bodey, Ti Li Loo

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

DMDR, a daunorubicin derivative with a higher therapeutic index and lower cardiotoxicity than either the parent drug or doxorubicin, is active when given PO in experimental animals. We studied its pharmacokinetics in ten patients receiving DMDR IV or PO or IV and PO sequentially at 10-12.5 mg/m2. DMDR and its metabolites were quantified by high-performance liquid chromatography and fluorometry. In nine patients who received DMDR IV the unchanged drug disappeared from the plasma biphasically with a mean terminal half-life of 27.0±5.5 h, an apparent volume of distribution of 63.9±12.61 kg-1, and a total clearance of 1.9±0.41 kg-1 h-1. In 24 h only 5.1%±1.1% of the dose was excreted in the urine. In comparison, in 19 studies the plasma half-life of DMDR given PO was 34.8±6.7 h, 2.3%±1.3% was excreted in the urine in 24 h, and the maximum plasma drug concentration was reached in about 1 h. The bioavailability of DMDR given PO was about 39% according to comparison of the areas under the plasma DMDR concentration versus time curves for the two routes, but 45% according to comparison of the 24-h cumulative urinary excretion rates. In one patient with severe liver dysfunction following oral administration, the plasma DMDR half-life was 56.8 h, more than twice the average length. By either route, the drug was quickly metabolized to one major metabolite, DMDR-ol. The plasma half-life of DMDR-ol was 72.5±24.7 h, or 35.7±7.4 when DMDR was administered IV or PO. In the plasma, DMDR-ol always exceeded DMDR in concentration. Moreover, the 24 h cumulative urinary excretion of DMDR-ol as a percentage of the dose of DMDR administered was 7.8 following IV and 7.4 following PO administration.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume17
Issue number2
DOIs
StatePublished - Jun 1 1986
Externally publishedYes

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Idarubicin
Clinical Pharmacology
Plasmas
Half-Life
Metabolites
Pharmaceutical Preparations
Urine
Fluorometry
Daunorubicin
Pharmacokinetics
High performance liquid chromatography

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Clinical pharmacology of 4-demethoxydaunorubicin (DMDR). / Lu, Katherine; Savaraj, Niramol; Kavanagh, John; Feun, Lynn G; Burgess, Michael; Bodey, Gerald P.; Loo, Ti Li.

In: Cancer Chemotherapy and Pharmacology, Vol. 17, No. 2, 01.06.1986, p. 143-148.

Research output: Contribution to journalArticle

Lu, Katherine ; Savaraj, Niramol ; Kavanagh, John ; Feun, Lynn G ; Burgess, Michael ; Bodey, Gerald P. ; Loo, Ti Li. / Clinical pharmacology of 4-demethoxydaunorubicin (DMDR). In: Cancer Chemotherapy and Pharmacology. 1986 ; Vol. 17, No. 2. pp. 143-148.
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