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Cancer Chemotherapy and Pharmacology

, Volume 21, Issue 3, pp 221–228 | Cite as

Epirubicin and doxorubicin comparative metabolism and pharmacokinetics

A cross-over study
  • Carlo M. Camaggi
  • Raffaella Comparsi
  • Elena Strocchi
  • Fabio Testoni
  • Bruna Angelelli
  • Franco Pannuti
Original Articles Doxorubicin, Epirubicon, Metabolism, Pharmacokinetics

Summary

The pharmacokinetics and metabolism of doxorubicin (DX) and epirubicin (epiDX) were investigated in eight cancer patients who received 60 mg/m2 of both drugs independently by intravenous (i.v.) bolus at 3-week intervals according to a balanced cross-over design. Unchanged DX and epiDX plasma levels followed a triexponential decay. Half-lives (t/2) of the three decay phases were longer for DX (t/2α: 4.8 vs. 3 min; t/2β 2.57 h vs. 1.09 h; t/2γ 48.4 vs. 31.2 h). According to a model-independent analysis, the different plasma disposition kinetics of the two compounds appears to be related to a higher plasma clearance (PlCl) and to a lower mean residence time (MRT) of epiDX (PlCl: 75.0 l/h, range: 35.6–133.4 l/h; MRT: 31.6 h, range: 7.0–41.5 h;) compared to DX (PlCl: 56.8 l/h, range: 24.4–119.5; MRT: 45.6 h, range: 26.0–83.1 h). No statistically significant differences could be detected for the volume of distribution at steady state (Vss) (epiDX, 31.8 l/kg; DX, 33.3 l/kg). Metabolites common to both compounds were detected in plasma: the 13-dihydro derivatives doxorubicinol (DXol) and epirubicinol (epiDXol), together with monor amounts of four aglycones (7-deoxy adriamycinone, adriamycinone, 7-deoxy 13-dihydro adriamycinone, and 13-dihydro adriamycinone). Following epiDX administration, two additional major metabolites were detected: the glucuronic acid conjugates of epiDX (4′-O-β-d-glucuronyl-4′-epiDX) and epiDXol (4′-O-β-d-glucuronyl 13-dihydro-4′-epiDX). This additional detoxication route appears to account for the more efficient and faster elimination of epiDX than of DX. In the urine collected in the 6 days after treatment, 12.2% of the DX and 11.9% of the epiDX dose was excreted as unchanged drug and fluorescent metabolites. A comparable renal clearance was calculated for DX (4.7 l/h, range 1.4–7.0 l/h) and epiDX (4.4 l/h, range 1.7–7.0 l/h). One patient with hepatic metastates and abnormal bilirubin serum level had percutaneous biliary drainage because of extrahepatic obstruction. The elimination of both drugs was significantly impaired in this patient; nevertheless, elimination of epiDX was still more efficient and faster than that of DX (PlCl: 35.6 vs. 24.4 l/h; MRT: 39.0 vs. 83.1 h; t/2γ: 47 vs. 74 h). This patient's biliary excretion accounted for 35.4% of the epiDX dose and 18.2% of the DX dose.

Keywords

Epirubicin Glucuronic Acid Mean Residence Time Percutaneous Biliary Drainage Glucuronic Acid Conjugate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Carlo M. Camaggi
    • 1
  • Raffaella Comparsi
    • 1
  • Elena Strocchi
    • 2
  • Fabio Testoni
    • 1
  • Bruna Angelelli
  • Franco Pannuti
  1. 1.Dipartimento di Chimica Organica dell'Universita'BolognaItaly
  2. 2.Divisione di OncologiaOspedale M. MalpighiBolognaItaly

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