Pharmacokinetics of intravenously administered stealth liposomal doxorubicin modulated with verapamil in rats

Jian Cheng Wang, Xiao Yan Liu, Wan Liang Lu, Alex Y Chang, Qiang Zhang, Boon Cher Goh, How Sung Lee

Research output: Contribution to journalArticle

Abstract

Treatment of cancer through co-administration of anticancer drugs and multidrug resistance (MDR) modulators as a strategy to overcome drug resistance has been extensively explored. However, success has been limited by pharmacokinetic interactions because of non-specific blockade of P-glycoprotein (P-gp) in normal tissues or inability to reach relevant concentrations clinically. We hypothesized that stealth liposomal co-encapsulation of doxorubicin (DOX) with a P-glycoprotein inhibitor, verapamil (DARSLs), may overcome these limitations. Using intravenous (i.v.) administrations, the effects of verapamil (VER) either free (FV) or liposome co-encapsulated with DOX (DARSLs) on the pharmacokinetics and tissue distribution characteristics of DOX either as free (FD) or liposome-encapsulated (LD) were evaluated in normal rats. FV increased (P

Original languageEnglish (US)
Pages (from-to)44-51
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume62
Issue number1
DOIs
Publication statusPublished - Jan 2006
Externally publishedYes

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Keywords

  • Biodistribution
  • Doxorubicin
  • Pharmacokinetics
  • Stealth liposomes
  • Verapamil

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

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