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Effects of adamantyl derivatives on pharmacokinetic behavior of paclitaxel in rats

Title
Effects of adamantyl derivatives on pharmacokinetic behavior of paclitaxel in rats
Authors
Kim K.M.Lee K.Jang K.Moon Y.S.Lee H.J.Rhie S.J.
Ewha Authors
이화정이정연
SCOPUS Author ID
이화정scopus; 이정연scopus
Issue Date
2017
Journal Title
Biomolecules and Therapeutics
ISSN
1976-9148JCR Link
Citation
vol. 25, no. 5, pp. 553 - 558
Keywords
Adamantyl derivativesOral bioavailabilityP-glycoproteinPaclitaxelVerapamil
Publisher
Korean Society of Applied Pharmacology
Indexed
SCIE; SCOPUS; KCI WOS scopus
Abstract
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. © 2017 The Korean Society of Applied Pharmacology.
DOI
10.4062/biomolther.2016.191
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약학대학 > 약학과 > Journal papers
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