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Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics

Title
Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics
Authors
Lee, JaeokChae, Song WhaOh, A. ReumYoo, Ji HyeChoo, Hea-Young ParkRhie, Sandy JeongLee, Hwa Jeong
Ewha Authors
박혜영이화정이정연
SCOPUS Author ID
박혜영scopus; 이화정scopus; 이정연scopus
Issue Date
2019
Journal Title
PHARMACEUTICS
ISSN
1999-4923JCR Link
Citation
PHARMACEUTICS vol. 11, no. 1
Keywords
piperazine derivativesP-glycoprotein inhibitorpharmacokineticsbioavailabilitypaclitaxel
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
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.
DOI
10.3390/pharmaceutics11010023
Appears in Collections:
약학대학 > 약학과 > Journal papers
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