title: Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer.
abstract: 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.
authors.affiliation: Pediatric Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Berg
authors.forename: A
authors.initials: A
authors.lastname: Tolcher
authors.forename: J A
authors.initials: JA
authors.lastname: O'Shaughnessy
authors.forename: A M
authors.initials: AM
authors.lastname: Denicoff
authors.forename: M
authors.initials: M
authors.lastname: Noone
authors.forename: F P
authors.initials: FP
authors.lastname: Ognibene
authors.forename: K H
authors.initials: KH
authors.lastname: Cowan
authors.forename: F M
authors.initials: FM
authors.lastname: Balis
mesh_terms: 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*
chemical_list: D014700:Verapamil; D017239:Paclitaxel