Scutellarin is Highly Likely to be Responsible for Drug-Drug Interactions Mediated by Hepatic Organic Anion-Transporting
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RESEARCH PAPER
Scutellarin is Highly Likely to be Responsible for Drug-Drug Interactions Mediated by Hepatic Organic Anion-Transporting Polypeptide1B3 Jianming Liu 1 & Yongmei Guo 2 & Yanqi Xu 2 & Li Yuan 3 & Huiting Zhu 4,5
Received: 28 July 2020 / Accepted: 7 October 2020 # The Author(s) 2020
ABSTRACT Purpose Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T cells expressing human organic anion transporting polypeptide 1B3 (hOATP1B3) and rat OATP1B2 (rOATP1B2), respectively, and the effect of scutellarin on the pharmacokinetics of rosuvastatin in rats. Methods The newly established HEK293T cells expressing hOATP1B3 and rOATP1B2 were used to examine the effects of scutellarin and positive controls on in vitro rosuvastatin transport. After co-feeding with scutellarin, the rosuvastatin area under the plasma concentration-time curve (AUC0–24h), the peak plasma drug concentration (Cmax), elimination halflife (t1/2), time to reach Cmax (tmax), clearance (CL) and apparent clearance (CL/F) of rosuvastatin were determined in rats.
Jianming Liu and Yongmei Guo contributed equally to this work. * Jianming Liu [email protected] * Huiting Zhu [email protected] 1
School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330031, People’s Republic of China
2
School of Pharmacy, Jiangxi Medical College, Shangrao, Jiangxi 334000, People’s Republic of China
3
Department of Pharmacy, Ji’an Maternal and Child Health Hospital, Ji’an, Jiangxi 343000, People’s Republic of China
4
Pharmacy Department, The Affiliated Children’s Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China
5
Pharmacy Department, Jiangxi Provincial Children’s Hospital, Nanchang, Jiangxi 330006, People’s Republic of China
Results Scutellarin inhibited hOATP1B3- and rOATP1B2mediated rosuvastatin uptake (IC50: 45.54 ± 6.67 μM and 27.58 ± 3.97 μM) in vitro in a concentration-dependent manner. After co-feeding with scutellarin, the AUC0–24h and Cmax of rosuvastatin in rats increased to 27.4% and 37.7%, respectively. The t1/2 and tmax of rosuvastatin showed no significant change. Moreover, scutellarin caused 29.2% and 28.1% decrease in the CL and CL/F of rosuvastatin. Conclusion Scutellarin may inhibit the hOATP1B3- and rOATP1B2-mediated transport of rosuvastatin in vitro, and exerts a moderate inhibitory effect on the pharmacokinetics of rosuvastatin in rats. Scutellarin is highly likely to participate in drug-drug interactions, as mediated by OATP1B3 in humans.
KEY WORDS drug-drug interactions (DDI) . organic anion transporting polypeptide 1B3 (OATP1B3) . rosuvastatin . scutellarin
ABBREVIATIONS AUC Cmax CL CL/F DDI GA LC/MS/ MS OATP RSV RIF SCU tmax t1/2 CMC-Na
Area under the plasma concentration-time curve Peak plasma drug concentration Clearance Apparent cl
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