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 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.