We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics.
- Authors
Lee, Jaeok; Chae, Song Wha; Oh, A Reum; Yoo, Ji Hye; Park Choo, Hea-Young; Rhie, Sandy Jeong; Lee, Hwa Jeong
- 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 AUCinf of PTX without alterations in the Cmax value. The elimination half-life was extended and the oral clearance decreased. Additionally, the Tmax 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.
- Subjects
P-glycoprotein; PIPERAZINE; PACLITAXEL; CANCER cells; PHARMACOKINETICS
- Publication
Pharmaceutics, 2019, Vol 11, Issue 1, p23
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics11010023