Pharmacokinetics of eribulin mesylate in patients with solid tumours receiving repeated oral rifampicin

Lot A. Devriese, Petronella O. Witteveen, Jantien Wanders, Kenneth Law, Geoff Edwards, Larisa Reyderman, William Copalu, Fuping Peng, Serena Marchetti, Jos H. Beijnen, Alwin D.R. Huitema, Emile E. Voest, Jan H.M. Schellens

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

17 Citaten (Scopus)


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 1.4mgm-2 eribulin mesylate on days 1 and 15 and oral rifampicin 600mg on days 9 to 20 of a 28day cycle. Pharmacokinetic sampling for determination of eribulin plasma concentrations was performed up to 144h following administration. AUC(0,∞) and Cmax 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 1.4mgm-2 eribulin mesylate on days 1 and 8 of a 21day 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 Cmax = 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.

Originele taal-2Engels
Pagina's (van-tot)507-521
Aantal pagina's15
TijdschriftBritish Journal of Clinical Pharmacology
Nummer van het tijdschrift2
StatusGepubliceerd - feb. 2013
Extern gepubliceerdJa


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