Effect of coumarin derivative-mediated inhibition of P-glycoprotein on oral bioavailability and therapeutic efficacy of paclitaxel
- 주제(키워드) Coumarin derivative , P-glycoprotein , Daunomycin , Paclitaxel , Bioavailability , Xenograft
- 등재 SCIE, SCOPUS
- 발행기관 ELSEVIER SCIENCE BV
- 발행년도 2014
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000087116
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.ejphar.2013.11.002
초록/요약
Since P-glycoprotein (P-gp) acts as a barrier to intestinal absorption of various drugs, P-gp inhibitors have been studied as oral absorption enhancers of P-gp substrate drugs. Here, we investigated the in vitro and in vivo effects of a novel coumarin derivative (LL-348) for its P-gp inhibitory activity. With LL-348, accumulation of daunomycin (DNM) increased 270% and efflux of DNM decreased 63% compared to that of DNM alone. Paclitaxel (PTX, 25 mg/kg) after oral administration with LL-348 (5 mg/kg), the optimal dose of LL-348 as an oral absorption enhancer of PTX, improved the relative bioavailability (RB) of PTX to 961%. In a xenograft animal model, PTX (40 mg/kg) treated with LL-348 (10 mg/kg) significantly increased the efficacy of PTX. The results collectively demonstrate that LL-348 can provide a therapeutic benefit in the oral absorption of P-gp substrate anticancer drugs (C) 2013 Elsevier B.V. All rights reserved
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