EFFECT OF R-VERAPAMIL ON THE PHARMACOKINETICS OF PACLITAXEL IN WOMEN WITH BREAST-CANCER

Purpose: To study the effect of the multidrug-resistance reversal agent R-verapamil on the pharmacokinetic behavior of poclitaxel. 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 clearonce from 179 +/- 67 mL/min/m(2) to 90 +/- 34 mL/min/m(2) (P < .03) and in a twofold increase in paclitaxel exposure (area under the curve [AUG]). The mean end-infusion paclitaxel concentration was also twofold higher: 5.1 +/- 1.8 mu mol/L versus 11.3 +/- 4.1 mu mol/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. (C) 1995 by American Society of Clinical Oncology.