Tsai Pi-Lo, Tsai Tung-Hu
National Research Institute of Chinese Medicine, 155-1, Li-Nong Street Section 2, Shih-Pai, Taipei 112, Taiwan.
Drug Metab Dispos. 2004 Apr;32(4):405-12. doi: 10.1124/dmd.32.4.405.
Berberine is a bioactive herbal ingredient isolated from the roots and bark of Berberis aristata or Coptis chinensis. To investigate the detailed pharmacokinetics of berberine and its mechanisms of hepatobiliary excretion, an in vivo microdialysis coupled with high-performance liquid chromatography was performed. In the control group, rats received berberine alone; in the drug-treated group, 10 min before berberine administration, the rats were injected with cyclosporin A (CsA), a P-glycoprotein (P-gp) inhibitor; quinidine, both organic cation transport (OCT) and P-gp inhibitors; SKF-525A (proadifen), a cytochrome P450 inhibitor; and probenecid to inhibit the glucuronidation. The results indicate that berberine displays a linear pharmacokinetic phenomenon in the dosage range from 10 to 20 mg kg(-1), since a proportional increase in the area under the concentration-time curve (AUC) of berberine was observed in this dosage range. Moreover, berberine was processed through hepatobiliary excretion against a concentration gradient based on the bile-to-blood distribution ratio (AUC(bile)/AUC(blood)); the active berberine efflux might be affected by P-gp and OCT since coadministration of berberine and CsA or quinidine at the same dosage of 10 mg kg(-1) significantly decreased the berberine amount in bile. In addition, berberine was metabolized in the liver with phase I demethylation and phase II glucuronidation, as identified by liquid chromatography/tandem mass spectrometry. Also, the phase I metabolism of berberine was partially reduced by SKF-525A treatment, but the phase II glucuronidation of berberine was not obviously affected by probenecid under the present study design.
黄连素是从刺檗或黄连的根和树皮中分离出来的一种具有生物活性的草药成分。为了研究黄连素详细的药代动力学及其肝胆排泄机制，进行了一项体内微透析结合高效液相色谱的实验。在对照组中，大鼠单独接受黄连素；在药物治疗组中，在给予黄连素前10分钟，给大鼠注射环孢素A（CsA），一种P-糖蛋白（P-gp）抑制剂；奎尼丁，有机阳离子转运体（OCT）和P-gp抑制剂；SKF-525A（丙胺卡因），一种细胞色素P450抑制剂；以及丙磺舒以抑制葡萄糖醛酸化。结果表明，黄连素在10至20mg kg⁻¹的剂量范围内呈现线性药代动力学现象，因为在此剂量范围内观察到黄连素浓度-时间曲线下面积（AUC）成比例增加。此外，根据胆汁与血液分布比（AUC(胆汁)/AUC(血液)），黄连素通过肝胆排泄逆浓度梯度进行；活性黄连素外排可能受P-gp和OCT影响，因为以相同剂量10mg kg⁻¹同时给予黄连素和CsA或奎尼丁会显著降低胆汁中黄连素的含量。此外，通过液相色谱/串联质谱鉴定，黄连素在肝脏中经I相去甲基化和II相葡萄糖醛酸化代谢。而且，在本研究设计下，SKF-525A处理可部分降低黄连素的I相代谢，但丙磺舒对黄连素的II相葡萄糖醛酸化没有明显影响。
