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)
| Autor: | R. F. M. Rombouts, Auke Bult, Jos H. Beijnen, R. van Gijn, W.W. ten Bokkel Huinink, Hilde Rosing |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Biological Availability Antineoplastic Agents Breast Neoplasms Pharmacology Bioequivalence study Pharmacokinetics medicine Humans Drug Interactions Pharmacology (medical) Doxorubicin In patient Cyclophosphamide Chromatography High Pressure Liquid Dexrazoxane Hydrochloride Aged Cross-Over Studies business.industry Cancer Middle Aged medicine.disease Fluorouracil Female Dexrazoxane Razoxane business medicine.drug |
| Zdroj: | European Journal of Drug Metabolism and Pharmacokinetics. 24:69-77 |
| ISSN: | 2107-0180 0378-7966 |
| Popis: | 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 concentration versus 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, t1/2beta, Vdss, Cl(tot), Cl(ren)). 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 (t1/2beta, Cl(tot) and Cl(ren)). |
| Databáze: | OpenAIRE |
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