Effects of piperazine derivative on paclitaxel pharmacokinetics

Jaeok Lee, Song Wha Chae, A. Reum Oh, Ji Hye Yoo, Hea Young Park Choo, Sandy Jeong Rhie, Hwa Jeong Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Paclitaxel (PTX) is an anticancer agent that is used to treat many cancers but it has a very low oral bioavailability due, at least in part, to the drug efflux transporter, P-glycoprotein (P-gp). Therefore, this study was performed to enhance oral bioavailability of PTX. In this study, we investigated the effects of several piperazine derivatives on P-gp function in vitro. Compound 4 was selected as the most potent P-gp inhibitor from the in vitro results for examining the pharmacokinetic (PK) changes of PTX in rats. Compound 4 increased the AUC inf of PTX without alterations in the C max value. The elimination half-life was extended and the oral clearance decreased. Additionally, the T max was delayed or widened in the treatment groups. Therefore, the bioavailability (BA) of PTX was improved 2.1-fold following the co-administration of 5 mg/kg of the derivative. A piperazine derivative, compound 4, which was confirmed as a substantial P-gp inhibitor in vitro increased the BA of PTX up to 2-fold by a lingering absorption, in part due to inhibition of intestinal P-gp and a low oral clearance of PTX. These results suggest that co-administering compound 4 may change the PK profile of PTX by inhibiting P-gp activity in the body.

Original languageEnglish
Article number23
Issue number1
StatePublished - 1 Jan 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


  • Bioavailability
  • P-glycoprotein inhibitor
  • Paclitaxel
  • Pharmacokinetics
  • Piperazine derivatives


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