Aim: Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that was recently approved for treatment of metastatic breast cancer. The aim of this study was to determine the effect of rifampicin, a CYP3A4 inducer, on the plasma pharmacokinetics of eribulin in patients with solid tumours.
Methods: An open-label, non-randomized phase I study was carried out. Patients received intravenous 1.4 mg m(-2) eribulin mesylate on days 1 and 15 and oral rifampicin 600 mg on days 9 to 20 of a 28 day cycle. Pharmacokinetic sampling for determination of eribulin plasma concentrations was performed up to 144 h following administration. AUC(0,∞) and C(max) for eribulin exposure without or with co-administration of rifampicin were subjected to an analysis of variance (anova) and corresponding 90% confidence intervals (CI) were calculated. Subsequently, patients were allowed to continue eribulin mesylate treatment with 1.4 mg m(-2) eribulin mesylate on days 1 and 8 of a 21 day cycle. Also the adverse event profile and anti-tumour activity were assessed.
Results: Fourteen patients were included and 11 patients were evaluable for pharmacokinetic analysis. Co-administration of rifampicin had no effect on single dose exposure to eribulin (geometric least square means ratio: AUC(0,∞) = 1.10, 90% CI 0.91, 1.34 and C(max) = 0.97, 90% 0.81, 1.17). The most common treatment-related grade ≥3 adverse events were grade 3 neutropenia (4/14, 29%), leucopenia and fatigue (both 3/14, 21%).
Conclusions: These results indicate that eribulin mesylate may be safely co-administered with compounds that are CYP3A4 inducers.
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.