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

Research output: Contribution to journalArticle

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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
StatePublished - Jan 1 1995

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Verapamil
Paclitaxel
Pharmacokinetics
Breast Neoplasms
Multiple Drug Resistance
Drug Combinations
Reverse-Phase Chromatography
Area Under Curve
High Pressure Liquid Chromatography
Clinical Trials

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

Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer. / Berg, Stacey L.; Tolcher, Anthony; O'Shaughnessy, Joyce A.; Denicoff, Andrea M.; Noone, Marianne; Ognibene, Frederick P.; Cowan, Kenneth H; Balis, Frank M.

In: Journal of Clinical Oncology, Vol. 13, No. 8, 01.01.1995, p. 2039-2042.

Research output: Contribution to journalArticle

Berg, SL, Tolcher, A, O'Shaughnessy, JA, Denicoff, AM, Noone, M, Ognibene, FP, Cowan, KH & Balis, FM 1995, 'Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer', Journal of Clinical Oncology, vol. 13, no. 8, pp. 2039-2042. https://doi.org/10.1200/JCO.1995.13.8.2039
Berg SL, Tolcher A, O'Shaughnessy JA, Denicoff AM, Noone M, Ognibene FP et al. Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer. Journal of Clinical Oncology. 1995 Jan 1;13(8):2039-2042. https://doi.org/10.1200/JCO.1995.13.8.2039
Berg, Stacey L. ; Tolcher, Anthony ; O'Shaughnessy, Joyce A. ; Denicoff, Andrea M. ; Noone, Marianne ; Ognibene, Frederick P. ; Cowan, Kenneth H ; Balis, Frank M. / Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer. In: Journal of Clinical Oncology. 1995 ; Vol. 13, No. 8. pp. 2039-2042.
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