Acta Pharm. 66 (2016) 97-107
Original research paper
Effect of quercetin
on the transport of ritonavir to the central nervous
system in vitro and in vivo
GONGWEN
LIANG, NA LI, LIPING MA,
ZHONGLIAN
QIAN, YUWEN SUN, LUWEN SHI and LIBO ZHAO
shilu@bjmu.edu.cn; libozhao2011@163.com
1 School of Pharmaceutical Sciences, Peking
University, Beijing 100191, China
2 Institute of
Clinical Molecular Biology, Peking University People’s Hospital, Beijing
100044, China
3 School of
Pharmacy, Guiyang Medical University, Guiyang 550004,
China
4 Department
of Pharmacy, Peking University People’s Hospital,
Beijing 100044, China
Accepted September 28, 2015
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 level of ritonavir was increased in the presence of 25 mmol L–1of 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.
Keywords: quercetin, flavonoids, ritonavir,
blood-brain barrier, pharmacokinetics