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Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics
- Title
- Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics
- Authors
- Lee, Jaeok; Chae, Song Wha; Oh, A. Reum; Yoo, Ji Hye; Choo, Hea-Young Park; Rhie, Sandy Jeong; Lee, Hwa Jeong
- Ewha Authors
- 박혜영; 이화정; 이정연
- SCOPUS Author ID
- 박혜영; 이화정; 이정연
- Issue Date
- 2019
- Journal Title
- PHARMACEUTICS
- ISSN
- 1999-4923
- Citation
- PHARMACEUTICS vol. 11, no. 1
- Keywords
- piperazine derivatives; P-glycoprotein inhibitor; pharmacokinetics; bioavailability; paclitaxel
- Publisher
- MDPI
- Indexed
- SCIE; 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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