<abstract xmlns="http://www.w3.org/1999/xhtml">The aim of this study was to identify an effective flavonoid that could improve the intracellular accumulation of ritonavir in human brain-microvascular endothelial cells (HBMECs). An <italic>in vivo</italic> experiment on Sprague-Dawley rats was then designed to further determine the flavonoid’s impact on the pharmacokinetics and tissue distribution of ritonavir. In the accumulation assay, the intracellular leve l of ritonavir was increased in the presence of 25 mmol L−1 of flavonoids in HBMECs. Quercetin showed the strongest effect by improving the intracellular accumulation of ritonavir by 76.9 %. In the pharmacokinetic study, the presence of quercetin in the co-administration group and in the pretreatment group significantly decreased the area under the plasma concentration-time curve (<italic>AUC</italic>0–t) of ritonavir by 42.2 % (<italic>p</italic> &lt; 0.05) and 53.5 % (<italic>p</italic> &lt; 0.01), and decreased the peak plasma concentration (<italic>c</italic>max) of ritonavir by 23.1 % (<italic>p</italic> &lt; 0.05) and 45.8 % (<italic>p</italic> &lt; 0.01), respectively, compared to the control group (ritonavir alone). In the tissue distribution study, the ritonavir concentration in the brain was significantly increased 2-fold (<italic>p</italic> &lt; 0.01), during the absorption phase (1 h) and was still significantly higher (<italic>p</italic> &lt; 0.05) during the distribution phase (6 h) in the presence of quercetin.</abstract>

The aim of this study was to identify an effective flavonoid that could improve the intracellular accumulation of ritonavir in human brain-microvascular endothelial cells (HBMECs). An in vivo experiment on Sprague-Dawley rats was then designed to further determine the flavonoid’s impact on the pharmacokinetics and tissue distribution of ritonavir. In the accumulation assay, the intracellular leve l of ritonavir was increased in the presence of 25 mmol L−1 of flavonoids in HBMECs. Quercetin showed the strongest effect by improving the intracellular accumulation of ritonavir by 76.9 %. In the pharmacokinetic study, the presence of quercetin in the co-administration group and in the pretreatment group significantly decreased the area under the plasma concentration-time curve (AUC0–t) of ritonavir by 42.2 % (p < 0.05) and 53.5 % (p < 0.01), and decreased the peak plasma concentration (cmax) of ritonavir by 23.1 % (p < 0.05) and 45.8 % (p < 0.01), respectively, compared to the control group (ritonavir alone). In the tissue distribution study, the ritonavir concentration in the brain was significantly increased 2-fold (p < 0.01), during the absorption phase (1 h) and was still significantly higher (p < 0.05) during the distribution phase (6 h) in the presence of quercetin.

Effect of quercetin on the transport of ritonavir to the central nervous system <italic>in vitro</italic> and <italic>in vivo</italic>

School of Pharmaceutical Sciences, Peking University, Beijing 100191 China

Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China

School of Pharmacy, Guiyang Medical University, Guiyang 550004, China

Department of Pharmacy, Peking University People’s Hospital, Beijing 100044, China

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Effect of quercetin on the transport of ritonavir to the central nervous system  and 

The aim of this study was to identify an effective flavonoid that could improve the intracellular accumulation of ritonavir in human brain-microvascular...

Effect of quercetin on the transport of ritonavir to the central nervous system in vitro and in vivo

Published Online: Mar 07, 2016

Page range: 97 - 107

Accepted: Sep 28, 2015

DOI: https://doi.org/10.1515/acph-2016-0009

Keywords
quercetin, flavonoids, ritonavir, blood-brain barrier, pharmacokinetics

© 2016 Gongwen Liang et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Effect of quercetin on the transport of ritonavir to the central nervous system in vitro and in vivo

Published Online: Mar 07, 2016

Page range: 97 - 107

Accepted: Sep 28, 2015

DOI: https://doi.org/10.1515/acph-2016-0009

Keywordsquercetin, flavonoids, ritonavir, blood-brain barrier, pharmacokinetics

© 2016 Gongwen Liang et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
quercetin, flavonoids, ritonavir, blood-brain barrier, pharmacokinetics