Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer.
OBJECTIVE
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 mumol/L versus 11.3 +/- 4.1 mumol/L (P < .03).


CONCLUSIONS
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.
Berg
S L
SL
Pediatric Branch, National Cancer Institute, Bethesda, MD, USA.
Tolcher
A
A
O'Shaughnessy
J A
JA
Denicoff
A M
AM
Noone
M
M
Ognibene
F P
FP
Cowan
K H
KH
Balis
F M
FM
D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014700:Verapamil / Q000627:therapeutic use*
D014700:Verapamil; D017239:Paclitaxel