Effects of adamantyl derivatives on pharmacokinetic behavior of paclitaxel in rats

Kyung Mi Kim, Kyeong Lee, Kyusic Jang, Yae Seul Moon, Hwa Jeong Lee, Sandy Jeong Rhie

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the Pglycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

Original languageEnglish
Pages (from-to)553-558
Number of pages6
JournalBiomolecules and Therapeutics
Issue number5
StatePublished - Sep 2017

Bibliographical note

Publisher Copyright:
© 2017 The Korean Society of Applied Pharmacology.


  • Adamantyl derivatives
  • Oral bioavailability
  • P-glycoprotein
  • Paclitaxel
  • Verapamil


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