Evidence for the Conversion of Docetaxel into 7-Epidocetaxel in Patients Receiving Conventional Taxotere® Based Chemotherapy

Authors

  • Martin Czejka Division of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria
  • Ernst Ulsperger Hospital Hietzing, 5th Medical Department / Oncology, A-1130 Vienna, Austria
  • Heinz Schnait Ebewe Pharma, A-4866 Unterach / Attersee, Austria
  • Tamara Brumnik Division of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria
  • Joerg Schierholz Ebewe Pharma, A-4866 Unterach / Attersee, Austria
  • Philipp Buchner Division of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria
  • Richard Greil State Hospital Salzburg, III. Department for Internal Medicine, A-5020 Salzburg, Austria

DOI:

https://doi.org/10.6000/1927-7229.2014.03.02.1

Keywords:

Docetaxel, epidocetaxel, epimerization, patients, plasma, urine.

Abstract

 Purpose:Epimerization at the C7atom of the baccatin moiety is a common in-vitro pathway for all taxanes, including the natural precursor 10-deacetyl baccatin III and the antineoplastic drugs paclitaxel and docetaxel. To date this in-vitro epimerization of both drugs has been elucidated completely, but epimerization of docetaxel in patients during chemotherapy has not yet described. The goal of this study was to identify the epimer of docetaxel in plasma and urine of taxotere treated patients. Patients and Methods:12 patients suffering from mamma carcinoma, lung cancer or prostate cancer were treated with various docetaxel-based schedules. Blood samples were drawn before start of infusion, at the end of infusion and 20 min thereafter, urine was collected and pooled for 6 hours. Docetaxel and its epimer epidocetaxel were quantified by solid phase extraction and reversed phase HPLC. Results:In 8 of 12 patients epidocetaxel could be quantified in plasma at the end of infusion (range 0.05 - 0.54 µg/ml). 20 minutes later concentrations were below LOQ due to rapid distribution of docetaxel into tissue. In urine, epidocetaxel has been found in 7 of 12 patients (range 0.1 - 0.5 µg/ml). Conclusion: Epidocetaxel is a distinct docetaxel metabolite in man. So our knowledge, this is the first time that quantification of epidocetaxel in blood and urine of chemotherapy patients has been reported. This finding is important for designing of new docetaxel generic drugs and the development of new chemotherapeutic schedules using docetaxel. To date the in-vivo pharmacologic and toxic properties of the epimer remain unclear.

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Published

2014-04-07

How to Cite

Martin Czejka, Ernst Ulsperger, Heinz Schnait, Tamara Brumnik, Joerg Schierholz, Philipp Buchner, & Richard Greil. (2014). Evidence for the Conversion of Docetaxel into 7-Epidocetaxel in Patients Receiving Conventional Taxotere® Based Chemotherapy. Journal of Analytical Oncology, 3(2),  73–78. https://doi.org/10.6000/1927-7229.2014.03.02.1

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