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


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


aclacinomycin A






thin layer chromatography


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


concentration times time


plasma concentration


Time after administration of drug


relative retardation factor


high performance liquid chromatography


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bachur NR, Gee M (1971) Daunorubicin metabolism by rat tissue preparations. J Pharmacol Exp Ther 177:567Google Scholar
  2. 2.
    Baker LH, Kessel DH, Comis RL, Reich SD, Defuria MD, Crooke ST (1979) American experience with carminomycin. Cancer Treat Rep 63:899Google Scholar
  3. 3.
    Benjamin RS, Riggs CE Jr, Bachur NR (1973) The pharmacokinetics and metabolism of adriamycin in man. Clin Pharmacol Ther 14:592Google Scholar
  4. 4.
    Benjamin RS, Riggs CE Jr, Bachur NR (1977) Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function. Cancer Res 37:1416Google Scholar
  5. 5.
    Blum RH, Garnick MB, Israel M, Canellos GP, Henderson IC, Frei E (1979) Initial clinical evaluation of N-trifluoroacetyladriamycin-14-valerate (AD 32) an adriamycin analog. Cancer Treat Rep 63:919Google Scholar
  6. 6.
    Bonfante V, Bonadonna G, Villani F, DiFronzo G, Martini A, Casazza AM (1979) Preliminary phase I study of 4′-epi-adria-mycin. Cancer Treat Rep 63:915Google Scholar
  7. 7.
    Cortes-Funes H, Gosalvez M, Moyano A, Manas A, Mendiola C (1979) Early clinical trial with quelamycin. Cancer Treat Rep 63:903Google Scholar
  8. 8.
    Crooke ST, Duvernay VH, Galvan L, Prestayko AW (1978) Structure-activity relationships of anthracyclines relative to effects on macromolecular syntheses. Mol Pharmacol 14:290Google Scholar
  9. 9.
    Di Carlo FJ (1980) Undifferentiated radioactivity revisited. Drug Metab Dispos 8:287Google Scholar
  10. 10.
    Egorin MJ, Clawson RE, Ross LA, Schlossberger NM, Bachur NR (1979) Cellular accumulation and disposition of aclacinomycin A. Cancer Res 39:4396Google Scholar
  11. 11.
    Egorin MJ, Van Echo DA, Whitacre MY, Fox BM, Aisner J, Wiernik PH, Bachur NR (1981) A phase I trial of aclacinomycin A. Proc AACR/ASCO 22:353Google Scholar
  12. 12.
    Fujimoto S, Inagaki J, Horikoshi N, Ogawa M (1979) Combination chemotherapy with a new anthracycline glycoside, aclacinomycin A, and active drugs for malignant lymphomas in P388 mouse leukemia system. Gan 70:411Google Scholar
  13. 13.
    Hori S, Shirai M, Hirano S, Oki T, Inui T, Tsukagoshi S, Ishizuka M, Takeuchi T, Umezawa H (1977) Antitumor activity of new anthracycline antibiotics, aclacinomycin-A and its analogs, and their toxicity. Gan 68:685Google Scholar
  14. 14.
    Jacquillat C, Weil M, Gemon-Auclerc MF, Izrael V, Bussel A, Boiron M, Bernard J (1976) Clinical study of rubidazone (22 050 R.P.) a new daunorubicin-derived compound in 170 patients with acute leukemias and other malignancies. Cancer 37:653Google Scholar
  15. 15.
    Jacquillat C, Auclerc MF, Weil M, Maral J, Degos L, Auclerc G, Tobelem G, Schaison G, Bernard J (1979) Clinical activity of detorubicin: A new anthracycline derivative. Cancer Treat Rep 63:889Google Scholar
  16. 16.
    Jansen ABA (1979) Total radioactivity half lives. Drug Metab Dispos 7:350Google Scholar
  17. 17.
    Kitamura I, Oki T, Inui T (1978) A sensitive analytical method for aclacinomycin A and its analogs by thin-layer chromatography and fluorescence scanning. J Antibiot (Tokyo) 31:919Google Scholar
  18. 18.
    Komiyama T, Oki T, Inui T (1979) A proposed reaction mechanism for the enzymatic reductive cleavage of glycosidic bond in anthracycline antibiotics. J Antibiot (Tokyo) 32:1219Google Scholar
  19. 19.
    Malspeis L, Neidhart J, Staubus A, Kear T, Booth J (1981) HPLC determination of aclacinomycin A (NSC 208734, Acm) in plasma and application to preliminary clinical pharmacokinetic studies. Proc Am Assoc Cancer Res 22:242Google Scholar
  20. 20.
    Mathé G, Bayssas M, Gouveia J, Dantchev D, Ribaud P, Machover D, Misset JL, Schwarzenberg L, Jasmin C, Hayat M (1978) Preliminary results of a phase II trial of aclacinomyin in acute leukemia and lymphosarcoma. Cancer Chemother Pharmacol 1:259Google Scholar
  21. 21.
    Ogasawara T, Masuda Y, Goto S, Oki T (1981) High performance liquid chromatographic determination of aclacinomycin A and its related compounds. II. Reverse phase HPLC determination of aclacinomycin A and its metabolites in biological fluids using fluorescence detection. J Antibiot (Tokyo) 34:52Google Scholar
  22. 22.
    Ogawa M, Inagaki J, Horikoshi N, Inoue K, Chinen T, Ueoka H, Nagura E (1979) Clinical study of aclacinomycin A. Cancer Treat Rep 63:931Google Scholar
  23. 23.
    Oki T (1977) New anthracycline antibiotics. J Antibiot (Tokyo) 30 [Suppl]: 570Google Scholar
  24. 24.
    Oki T, Matsuzawa Y, Yoshimoto A, Numata K, Kitamura I, Hori S, Takamatsu A, Umezawa H, Ishizuka M, Naganawa H, Suda H, Hamada M, Takeuchi T (1975) New antitumor antibiotics aclacinomycins A&B. J Antibiot (Tokyo) 28:830Google Scholar
  25. 25.
    Oki T, Takeuchi T, Oka S, Umezawa H (1980) Current status of Japanese studies with the new anthracycline antibiotic, aclacinomycin A. Recent Results Cancer 74:207Google Scholar
  26. 26.
    Oki T, Takeuchi T, Oka S, Umezawa H (1981) New anthracycline antibiotic aclacinomycin A: Experimental studies and correlations with clinical trials. Recent Results Cancer Res 76:21Google Scholar

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

Personalised recommendations