Tsai Pi-Lo, Tsai Tung-Hu
Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Planta Med. 2004 Nov;70(11):1069-74. doi: 10.1055/s-2004-832649.
Baicalin, a flavone glucuronide derived mainly from the root of Scutellaria baicalensis, has been used in traditional Chinese medicine as an anti-inflammatory and anti-viral agent. To explore whether the disposition of baicalin is related to multidrug resistance P-glycoprotein (P-gp), baicalin (3, 10 and 30 mg kg(-1); i. v.) was injected to rats for a pharmacokinetic study using microdialysis coupled with HPLC. The results indicate that baicalin goes through hepatobiliary excretion against a concentration gradient based on the blood-to-bile distribution ratio (AUCbile/AUCblood), but that AUCblood or AUCbile did not show any dose-related increase in the range from 3 to 30 mg kg(-1). Coadministration of cyclosporin A (CsA) or quinidine (both are P-gp inhibitors) was used to delineate the role of P-gp on baicalin disposition, while SKF-525A (a cytochrome P450 inhibitor) could specifically inhibit the cytochrome P450 catalysis of baicalin without crossing with P-gp function. Both CsA and quinidine promoted the active transport of baicalin into bile and reduced its level in blood, and this result was the same as that obtained by treating with SKF-525A. Hence, the association of the involvement of P-gp in active baicalin efflux into bile seems to be excluded since CsA and quinidine are also cytochrome P450 inhibitors. In addition, baicalin was not detected in the brain striatum after treating with baicalin alone in the present study. Also, neither CsA nor quinidine co-administered with baicalin is able to induce measurable levels of baicalin in rat brain, which suggests that baicalin might not be able to pass through the blood-brain barrier (BBB).
黄芩苷是一种主要从黄芩根部提取的黄酮葡萄糖醛酸苷，在传统中药中用作抗炎和抗病毒药物。为了探究黄芩苷的处置是否与多药耐药性P-糖蛋白（P-gp）有关，将黄芩苷（3、10和30mg/kg；静脉注射）注入大鼠体内，采用微透析结合高效液相色谱法进行药代动力学研究。结果表明，根据血胆汁分布比（AUCbile/AUCblood），黄芩苷通过肝胆排泄呈现逆浓度梯度，但在3至30mg/kg范围内，AUCblood或AUCbile均未显示出任何剂量相关的增加。联合使用环孢素A（CsA）或奎尼丁（两者均为P-gp抑制剂）来阐明P-gp在黄芩苷处置中的作用，而SKF-525A（一种细胞色素P450抑制剂）可特异性抑制黄芩苷的细胞色素P450催化作用，且不影响P-gp功能。CsA和奎尼丁均促进黄芩苷向胆汁的主动转运并降低其血液水平，这一结果与用SKF-525A处理所得结果相同。因此，由于CsA和奎尼丁也是细胞色素P450抑制剂，似乎可以排除P-gp参与黄芩苷向胆汁的主动外排。此外，在本研究中，单独给予黄芩苷后，在脑纹状体中未检测到黄芩苷。而且，与黄芩苷联合使用的CsA和奎尼丁均不能在大鼠脑中诱导出可测量水平的黄芩苷，这表明黄芩苷可能无法穿过血脑屏障（BBB）。
