Pharmacokinetic modeling of the blood-stable camptothecin analog AR-67 in two different formulations

Xiaoxi Liu, Eyob Adane, Fei Tang, Markos Leggas

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


AR-67 is a lipophilic camptothecin analog currently under clinical investigation using a Cremophor EL based formulation. However, as potential toxicity limitations exist in the clinical use of Cremophor, an alternative cyclodextrin (SBE-β-CD) based formulation has been proposed. Pharmacokinetic (PK) studies were conducted in mice and the SBE-β-CD based formulation was compared with the Cremophor EL formulation. PK studies were conducted following intravenous or oral administration of AR-67 in either Cremophor or SBE-β-CD formulation in mice. Noncompartmental analysis was used to determine the plasma and tissue drug distribution. A non-linear mixed effects (population) PK model was developed to fit both the oral and intravenous data and to estimate key PK parameters. The effect of formulation was explored as a covariate in the PK model. AR-67 in the SBE-β-CD formulation had similar plasma PK and biodistribution to that in the Cremophor EL formulation. The proposed two-compartment model described the plasma PK of AR-67 in both formulations adequately. AR-67 in the SBE-β-CD formulation exhibited dose linearity following both oral and intravenous administration. Our studies indicate that SBE-β-CD is a viable alternative to Cremophor EL as a pharmaceutical excipient for formulating AR-67.

Original languageEnglish
Pages (from-to)265-275
Number of pages11
JournalBiopharmaceutics and Drug Disposition
Issue number8
StatePublished - Sep 1 2019

Bibliographical note

Funding Information:
These studies were in part supported by the National Cancer Institute through NIH R21 award (CA-123867) to Markos Leggas.

Publisher Copyright:
© 2019 John Wiley & Sons, Ltd.


  • Cremophor EL
  • SBE-β-CD
  • camptothecin
  • pharmacokinetic modeling

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)


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