Title: | Polysorbate 20 alters the oral bioavailability of etoposide in wild type and mdr1a deficient Sprague-Dawley rats |
Author: | Al-Ali, AAA;Quach, JRC;Bundgaard, C;Steffansen, B;Holm, R;Nielsen, CU; |
Year: | 2018 |
Journal: | Int J Pharm |
Page: | 352-360 |
Volume: | 543 |
Issue: | 1-2 |
PubMed ID: | 29635055 |
Abstract: | The aim of the present work was to investigate the ability of nonionic surfactants to increase the oral absorption of the P-glycoprotein substrate etoposide in vitro and in vivo. Intestinal absorption was investigated by studying bidirectional permeability of etoposide across filter-grown Caco-2 and MDCKII MDR1 cell monolayers. The oral absorption of etoposide was investigated in wild type (WT) and mdr1a deficient (KO) Sprague-Dawley rats. In cell cultures, polysorbate 20 (PS20) decreased P-glycoprotein mediated efflux of etoposide. When PS20 and etoposide were co-administered to WT rats, the oral absorption of etoposide increased significantly in the presence of 5 and 25% (v/v) PS20. However, in KO rats, the exposure of etoposide after oral co-administration with 5% PS20 was similar to control. Unexpectedly, co-administration of etoposide with 25% PS20 significantly reduced the absorption fraction of etoposide in mdr1a KO rats. In vitro dialysis studies performed on PS20-containing etoposide solutions suggested that the reduced bioavailability may be due to etoposide retention in PS20 micelles and/or through increased viscosity. In conclusion, PS20 increases oral bioavailability of etoposide through inhibition of P-glycoprotein. However, the use of the excipient may be challenged by etoposide retention at higher concentrations. Copyright © 2018 Elsevier B.V. All rights reserved. |
Impact Factor: | 3.6 |
Link: | https://www.sciencedirect.com/science/article/pii/S0378517318302175 |
Date: | 5/30/2018 |
Email: | cun@sdu.dk |