Might adriamycinol contribute to adriamycin-induced cardiotoxicity?

Pharmacol Res Commun. 1985 Nov;17(11):1073-84. doi: 10.1016/0031-6989(85)90113-4.


The pharmacokinetics of adriamycin (ADR) and its 13-hydroxylated-metabolite adriamycinol (ADR-ol) was investigated during treatment with ADR in rats at a dose of 2 mg/kg i.v., once a week for 3 weeks. At various times, samples of blood and cardiac and pulmonary tissues were collected to measure the amount of ADR and ADR-ol by an HPLC procedure. Periodical ECG monitoring was performed during the study; the severity of cardiac lesions was histologically evaluated at the end of treatment. During the first 180 min after ADR administration, plasma levels of ADR and ADR-ol rapidly decreased; ADR levels in cardiac and in pulmonary tissues increased between the 15th and 30th min and than decreased between the 60th and 180th min; on the contrary, ADR-ol was undetectable in either cardiac or pulmonary tissues during the first 3 hours following ADR administration. Between the 1st and 3rd weeks of treatment, plasmatic levels of ADR and ADR-ol were unchanged; in a similar way, both cardiac and pulmonary tissue levels of ADR were constant during the period of treatment. By contrast, the cardiac tissue level of ADR-ol significantly increased between the 2nd and 3rd weeks. ECG tracings showed maximal enlargement of both QRS and S alpha T at the end of the 3rd week. The histological examination of cardiac tissue indicated the occurrence of degenerative changes in 20% of rats at the end of the experiment. Overall results seem to indicate that ADR-ol is produced and stored in cardiac tissue during repeated ADR administration; as a consequence the cytotoxic metabolite might contribute to the cardiotoxic effect of ADR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / metabolism
  • Doxorubicin / toxicity*
  • Electrocardiography
  • Heart Diseases / chemically induced*
  • Kinetics
  • Male
  • Rats
  • Rats, Inbred Strains
  • Time Factors


  • Doxorubicin
  • adriamycinol