Pharmacokinetics and disposition of (2''R)-4'-O-tetrahydropyranyladriamycin in dogs

Jpn J Antibiot. 1986 Feb;39(2):638-52.

Abstract

The pharmacokinetics and physiological disposition of a novel anthracyclines, (2''R)-4'-O-tetrahydropyranyladriamycin (THP) were studied in dogs by an HPLC analysis. The THP administered intravenously (1.5 mg/kg) disappeared rapidly from the plasma immediately after an injection of the drug. The plasma level of THP was lowered in a triphasic pattern up to 24 hours and was simulated by a three-compartment open model in which the half-lives of alpha-, beta- and gamma-phase were calculated to be 0.0116 hour, 0.152 hour and 7.02 hours, respectively. The blood cell level of THP was about 10 times as high as the plasma level during the observation. In the study of tissue distribution of THP 2 and 8 hours after the administration, the highest concentration of THP was found in the spleen and lung and these concentrations were diminished quickly. However, in the lymph nodes and bone marrow concentrations of THP increased with a lapse of time. THP and its metabolites were excreted in the bile by 2.7% of dose during 8 hours in the bile-cannulated dogs. Urinary recovery of THP and its metabolites was about 1.3% of the dose up to 72 hours. In these experiment, THP was metabolized to THP-OH and ADM, and to aglycones which were excreted in conjugated forms. The results obtained from a similar study on ADM were compared and discussed.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / blood
  • Antibiotics, Antineoplastic / metabolism*
  • Antibiotics, Antineoplastic / urine
  • Bile / metabolism
  • Dogs
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / blood
  • Doxorubicin / metabolism
  • Doxorubicin / urine
  • Kinetics
  • Tissue Distribution

Substances

  • Antibiotics, Antineoplastic
  • Doxorubicin
  • pirarubicin