Abstract
PurposeScutellarin, 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.MethodsThe 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 half-life (t1/2), time to reach Cmax (tmax), clearance (CL) and apparent clearance (CL/F) of rosuvastatin were determined in rats.ResultsScutellarin inhibited hOATP1B3- and rOATP1B2-mediated 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.ConclusionScutellarin 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.
Highlights
Traditional Chinese Medicine still plays an important role in protecting public health in countries like China and Japan [1]
After co-feeding with scutellarin, the AUC0–24h and Cmax of rosuvastatin in rats increased to 27.4% and 37.7%, respectively
Scutellarin is highly likely to participate in drug-drug interactions, as mediated by organic anion transporting polypeptide 1B3 (OATP1B3) in humans
Summary
Traditional Chinese Medicine still plays an important role in protecting public health in countries like China and Japan [1]. Various interactions between traditional Chinese medicine and drugs may occur, especially in the liver [7]. Transporters play a vital role in drug pharmacokinetics, and competing for them is crucial for drug uptake, distribution, and elimination [9,10]. The organic anion-transporting polypeptides (OATPs) may mediate DDI when drugs pass through the hepatic sinusoids [11]. Both genetic variation and DDI may change the transport function of human OATP1B1(hOATP1B1) and human OATP1B3(hOATP1B3) frequently trigger severe adverse events, for example, statin-induced rhabdomyolysis [12]. Considering that most hOATP1B1 inhibitors will inhibit hOATP1B3 clinically, SCU may be involved in DDI of these transporters
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