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Comparative open, randomized, cross-over bioequivalence study of two intravenous dexrazoxane formulations (Cardioxane® and ICRF-187) in patients with advanced breast cancer, treated with 5-fluorouracil-doxorubicin-cyclophosphamide (FDC)

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Summary

The purpose of this study was to compare the pharmacokinetic disposition of two intravenous dexrazoxane formulations, and their effects on doxorubicin’s kinetics and metabolism. Plasma concentrationversus time curves and pharmacokinetic parameters of dexrazoxane given as Cardioxane® (dexrazoxane hydrochloride salt) and ICRF-187 reference formulation (dexrazoxane base) were determined and compared. Both formulations were administered as a single intravenous infusion prior to 5-fluorouracil-doxorubicin-cyclophosphamide administration. In addition, the pharmacokinetics of doxorubicin and its metabolites were studied after dexrazoxane administration.

A total of 15 patients with advanced breast cancer participated in this open, randomized, cross-over study and 12 patients were evaluable. Plasma concentrations of dexrazoxane, doxorubicin and doxorubicin metabolites were determined by high-performance liquid chromatography in samples obtained in the 72 h after drug administration. No statistically significant differences were found in the tested kinetic parameters when the two products were compared by analysis of variance (ANOVA) on log-transformed data. Cardioxane® fulfilled the bioequivalence criteria when compared with ICRF-187 reference formulation for all of the investigated parameters (AUC, t1/2β, Vdss, Cltot, Clren). The parametric 90% confidence intervals were contained within the bioequivalence interval (0.8–1.25). Pharmacokinetic parameters and metabolism of doxorubicin were not different after the administration of either Cardioxane® or ICRF-187 formulation. From the results of this study it can be concluded that the two formulations can be considered bioequivalent with regard to extent of absorption (AUC and Vdss) and elimination (t1/2β, Cltot and Clren).

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Authors and Affiliations

  1. Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam

    W. W. Ten Bokkel Huinink & J. H. Beijnen

  2. Chiron BV, Amsterdam, The Netherlands

    R. F. M. Rombouts

  3. Department of Pharmaceutical Analysis and Toxicology, Faculty of Pharmacy, University of Utrecht, The Netherlands

    A. Bult & J. H. Beijnen

  4. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands

    H. Rosing, R. van Gijn & J. H. Beijnen

Authors
  1. H. Rosing
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  2. W. W. Ten Bokkel Huinink
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  3. R. van Gijn
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  4. R. F. M. Rombouts
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  5. A. Bult
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  6. J. H. Beijnen
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Rosing, H., Ten Bokkel Huinink, W.W., van Gijn, R. et al. Comparative open, randomized, cross-over bioequivalence study of two intravenous dexrazoxane formulations (Cardioxane® and ICRF-187) in patients with advanced breast cancer, treated with 5-fluorouracil-doxorubicin-cyclophosphamide (FDC). Eur. J. Drug Metab. Pharmacokinet. 24, 69–77 (1999). https://doi.org/10.1007/BF03190013

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  • DOI: https://doi.org/10.1007/BF03190013

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