Cancer Chemotherapy and Pharmacology

, Volume 8, Issue 1, pp 41–46 | Cite as

Plasma kinetics of aclacinomycin A and its major metabolites in man

  • Merrill J. Egorin
  • David Van Echo
  • Bonnie M. Fox
  • Margaret Whitacre
  • Nicholar R. Bachur
Original Articles Aclacinomycin A

Summary

The plasma pharmacokinetics of the antineoplastic anthracycline antibiotic aclacinomycin A (Acm) and its metabolites were studied in 12 patients treated with 60–120 mg/m2 during a phase I clinical trial. Total plasma drug fluorescence initially declined very rapidly, but from 2 to 24 h after injection, fluorescence rose progressively to intensities greater than those measured 1 min after Acm injection. Plasma total drug fluorescence slowly declined from 24 to 72 hours after Acm administration. These events reflected the rapid disappearance of Acm and the subsequent appearance of two highly fluorescent metabolites. One metabolite co-chromatographed with and had a fluorescence spectrum identical to known metabolite F1 (bisanhydroaklavinone). The other metabolite did not co-chromatograph with any previously described Acm metabolite. This metabolite had a fluorescence spectrum unlike any previously described Acm metabolite and was not altered by treatment for 60 min with 0.2N HCl at 100°C or by treatment for 24h at 37°C with bacterial β-glucuronidase or limpet aryl sulfatase.

Abbreviations used

Acm

aclacinomycin A

Dnr

daunorubicin

Ard

adriamycin

TLC

thin layer chromatography

MLAB

on-line modeling laboratory, Division of Computer Resources and Technology, National Institutes of Health

CxT

concentration times time

Cp

plasma concentration

t

Time after administration of drug

Rf

relative retardation factor

HPLC

high performance liquid chromatography

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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Merrill J. Egorin
    • 1
    • 2
  • David Van Echo
    • 1
    • 2
  • Bonnie M. Fox
    • 1
    • 2
  • Margaret Whitacre
    • 1
    • 2
  • Nicholar R. Bachur
    • 1
    • 2
  1. 1.Laboratory of Clinical Biochemistry, Baltimore Cancer Research ProgramDCT, NCIBaltimoreUSA
  2. 2.Clinical Oncology Branch, Baltimore Cancer Research ProgramDCT, NCIBaltimoreUSA

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