Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer

Stacey L. Berg, Anthony Tolcher, Joyce A. O'Shaughnessy, Andrea M. Denicoff, Marianne Noone, Frederick P. Ognibene, Kenneth H. Cowan, Frank M. Balis

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Abstract

Purpose: To study the effect of the multidrug-resistance reversal agent R- verapamil on the pharmacokinetic behavior of paclitaxel. Methods: Six women with breast cancer who received paclitaxel as a 3-hour infusion with and without R-verapamil were monitored with frequent plasma sampling up to 24 hours postinfusion. Paclitaxel concentrations were measured using a reverse- phase high-pressure liquid chromatography assay. Results: Concomitant administration of R-verapamil resulted in a decrease in mean (± SD) paclitaxel clearance from 179 ± 67 mL/min/m2 to 90 ± 34 mL/min/m2 (P < .03) and in a twofold increase in paclitaxel exposure (area under the curve [AUC]). The mean end-infusion paclitaxel concentration was also twofold higher: 5.1 ± 1.8 μmol/L versus 11.3 ± 4.1 μmol/L (P < .03). Conclusion: The alteration in paclitaxel pharmacokinetics when paclitaxel and R-verapamil are coadministered complicates the interpretation of response and toxicity data from clinical trials of this drug combination.

Original languageEnglish (US)
Pages (from-to)2039-2042
Number of pages4
JournalJournal of Clinical Oncology
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 1995

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Berg, S. L., Tolcher, A., O'Shaughnessy, J. A., Denicoff, A. M., Noone, M., Ognibene, F. P., ... Balis, F. M. (1995). Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer. Journal of Clinical Oncology, 13(8), 2039-2042. https://doi.org/10.1200/JCO.1995.13.8.2039