Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents

Ryan F. Schell, Brian J. Sidone, Whitney P. Caron, Mark D. Walsh, Taylor F. White, Beth A. Zamboni, Ramesh K. Ramanathan, William C. Zamboni

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Inter-patient PK variability of 9 liposomal and SM formulations of the same drug was evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range). CV% of AUC and AUC ranges were 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater, respectively, for liposomal compared with SM drugs. There was an inverse linear relationship between the clearance (CL) of liposomal agents and PK variability with a lower CL associated with greater PK variability (R2=0.39). PK variability of liposomal agents was greater when evaluated from 0-336h compared with 0-24h. PK variability of liposomes is significantly greater than SM. The factors associated with the PK variability of liposomal agents need to be evaluated. From the Clinical Editor: In this meta-analysis, the inter-patient pharmacokinetic variability of 9 liposomal and small molecule anti-cancer agents was studied. The authors determined that several parameters are in favor of the liposomal formulation; however, the PK variability of the formulation was higher compared with small molecule agents, the reason for which remains to be determined in future studies.

Original languageEnglish (US)
Pages (from-to)109-117
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • CKD-602
  • Liposomes
  • Pharmacokinetic
  • S-CKD602
  • Sampling schema
  • Variability

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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