Pharmacokinetics of eribulin mesylate in patients with solid tumours receiving repeated oral rifampicin. (10th January 2013)

• Record Type: Journal Article
• Authors: Devriese, Lot A.; Witteveen, Petronella (Els) O.; Wanders, Jantien; Law, Kenneth; Edwards, Geoff; Reyderman, Larisa; Copalu, William; Peng, Fuping; Marchetti, Serena; Beijnen, Jos H.; Huitema, Alwin D. R.; Voest, Emile E.; Schellens, Jan H. M.
• Is Part Of: British journal of clinical pharmacology. Volume 75:Number 2(2013:Feb.)
• Page Start: 507
• Page End: 521
• Publication Date: 2013-01-10
• Subjects: Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/j.1365-2125.2012.04381.x
• Languages: English
• ISSNs: 0306-5251

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bcp4381-sec-0001" sec-type="section"> <title>Aim</title> <p>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.</p> </sec> <sec id="bcp4381-sec-0002" sec-type="section"> <title>Methods</title> <p>An open‐label, non‐randomized phase I study was carried out. Patients received intravenous 1.4 mg m<sup>−2</sup> 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 <italic>C</italic><sub>max</sub> for eribulin exposure without or with co‐administration of rifampicin were subjected to an analysis of variance (<sc>anova</sc>) and corresponding 90% confidence intervals (CI) were calculated. Subsequently, patients were allowed to continue eribulin mesylate treatment with 1.4 mg m<sup>−2</sup> eribulin mesylate on days 1 and 8 of a 21 day cycle. Also the adverse event profile and anti‐tumour activity were assessed.</p> </sec> <sec id="bcp4381-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>C</italic><sub>max</sub> = 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%).</p> </sec> <sec id="bcp4381-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These results indicate that eribulin mesylate may be safely co‐administered with compounds that are CYP3A4 inducers.</p> </sec> </abstract>