Acta Pharmaceutica, Vol. 66 No. 1, 2016.
Izvorni znanstveni članak
https://doi.org/10.1515/acph-2016-0009
Effect of quercetin on the transport of ritonavir to the central nervous system in vitro and in vivo
GONGWEN LIANG
; School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
NA LI
; Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China
LIPING MA
; Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China
ZHONGLIAN QIAN
; School of Pharmacy, Guiyang Medical University, Guiyang 550004, China
YUWEN SUN
; School of Pharmacy, Guiyang Medical University, Guiyang 550004, China
LUWEN SHI
; School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
LIBO ZHAO
; Department of Pharmacy, Peking University People’s Hospital, Beijing 100044, China
Sažetak
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.
Ključne riječi
quercetin; flavonoids; ritonavir; blood-brain barrier; pharmacokinetics
Hrčak ID:
146010
URI
Datum izdavanja:
31.3.2016.
Posjeta: 1.332 *