Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis
Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis
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DOI：
10.1055/s-2004-815489
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发表时间：
2004-02-01
期刊：
影响因子：
2.7
通讯作者：
Chao, PDL
中科院分区：
文献类型：
--
作者：
Lai, MY;Hsiu, SL;Chao, PDL
黄芩为中药黄芩的根，临床应用广泛。为了研究SR对环孢素吸收和处置的影响，在随机交叉设计中，大鼠分别口服环孢素（以微乳Neoral（R）的形式）和静脉内同时给予和不同时给予SR煎剂。此外，主要成分的影响，例如，并研究了黄芩苷及其苷元黄芩素对环孢素在大鼠体内药代动力学的影响。采用特异性单克隆荧光偏振免疫法测定环孢素血药浓度。结果表明，参附水煎剂1 g/kg和2 g/kg剂量组的C-max分别降低62.9%和79.6%，AUC（0-540）分别降低55.2%和82.0%。与此相反，黄芩苷和黄芩素以112 mumol/kg的剂量联合给药时，环孢素的C-max分别显著增加408.1%和87.5%，AUC（0-540）分别增加685.3%和150.2%。然而，SR水煎剂并没有改变静脉环孢素的药代动力学。这些结果表明SR煎剂与环孢菌素在吸收部位发生了深刻的相互作用。为保证环孢素的有效性和安全性，应避免SR及其制剂与口服环孢素同时给药。
Scutellariae Radix (SR), the root of Scutellaria baicalensis (Labiatae), is widely used in clinical Chinese medicine. In order to investigate the effect of SR on the absorption and disposition of cyclosporine, rats were administered with cyclosporine orally (in the form of the microemulsion Neoral(R)) and intravenously with and without coadministration of SR decoction in randomized cross-over designs, respectively. Furthermore, the effects of the major constituents, e.g., baicalin and its aglycone baicalein on cyclosporine pharmacokinetics were also investigated in rats. A specific monoclonal fluorescence polarization immunoassay was used to determine the blood concentration of cyclosporine. Our results indicated that coadministration of SR decoction at doses of 1 g/kg and 2 g/kg significantly decreased the C-max of cyclosporine by 62.9% and 79.6% and reduced the AUC(0-540) by 55.2 % and 82.0 %, respectively. On the contrary, coadministration of baicalin and baicalein at doses of 112 mumol/kg markedly elevated the C-max of cyclosporine by 408.1% and 87.5% and increased the AUC(0-540) by 685.3 % and 150.2%, respectively. Nevertheless, SR decoction did not alter the pharmacokinetics of intravenous cyclosporine. These results indicate that a profound interaction between SR decoction and cyclosporine occurred at the absorption site. In order to ensure the efficacy and safety of cyclosporine, the coadministration of SR and its preparations with oral cyclosporine should be avoided.