Docetaxel in combination with epirubicin in metastatic breast cancer: pharmacokinetic interactions

Epirubicin (75 mg/m(2)) and docetaxel (75 mg/m(2)) were administered to 16 patients affected by metastatic breast cancer following two different sched ules: (1) docetaxel as infusion administered 1 h after epirubicin administr ation (schedule A); and (2) docetaxel as infusion immediately (10 min) afte r the end of epirubicin i.v. bolus administration (schedule B). Experimenta l non-compartmental analyses such as AUC and Css, were affected very little by the drug combination, irrespective of whether the administration of doc etaxel was immediately after the epirubicin bolus (10 min) or delayed (1 h) . However, serum levels showed evidence of transient drug interaction: in s chedule A, docetaxel infusion was associated with a transient increase of p lasma epirubicin in correspondence with Css(max) of docetaxel. Bi-compartme ntal analysis showed a significant difference in epirubicin clearance betwe en protocols A and B. It is suggested that polysorbate 80, used in minimal amounts to formulate docetaxel, may interfere with epirubicin plasma level. (C) 1999 Elsevier Science S.A. All rights reserved.