Development of a microdialysis system to monitor lamivudine in blood and liver for the pharmacokinetic application in herbal drug interaction and the gene expression in rats
Development of a microdialysis system to monitor lamivudine in blood and liver for the pharmacokinetic application in herbal drug interaction and the gene expression in rats
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DOI：
10.1016/j.jpba.2014.04.001
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发表时间：
2014-08-05
影响因子：
3.4
通讯作者：
Tsai, Tung-Hu
中科院分区：
文献类型：
--
作者：
Lu, Chia-Ming;Hou, Mei-Ling;Tsai, Tung-Hu
研究的目的是开发一种新型多重微透析技术，与经过验证的色谱系统相结合，用于测量未结合的蛋白质形式拉米夫定并研究其在大鼠血液和肝脏中的草药-药物相互作用。此外，通过微阵列分析评估了用传统中药制剂龙丹泻肝汤（LDXGT）治疗后大鼠体内药物代谢酶的基因表达变化。采用反相 C18 柱分离分析物，流动相为甲醇和 10 mM KH2PO4（15:85，v/v，用 NaOH 调节 pH 6.0），流速 0.8 mL/min，紫外波长设置为 270 nm。方法验证过程遵循食品和药物管理局 (FDA) 指南。药代动力学数据表明，拉米夫定给药（10mg/kg，静脉注射）后，单独拉米夫定和LDXGT预处理组的浓度-时间曲线下面积（AUC）在大鼠血液中分别为532+/-37.6和550+/-44.2minμg/mL，在大鼠肝脏中分别为682+/-196和642+/-153minμg/mL，分别。草药-药物药代动力学相互作用表明，单独使用拉米夫定或与 LDXGT 预处理联合使用，除了高剂量拉米夫定 (30 mg/kg) 的表观分布容积 (V-d) 外，药代动力学参数没有显着变化。此外，微阵列分析显示，在70个改变的基因中（选择标准：垂直条折叠变化垂直条> = 2且p<0.05），只有11个基因参与药物代谢，表明在治疗剂量的LDXGT治疗后，肝脏中相对较小部分的药物代谢基因在基因组水平上发生了改变。总之，这些研究为解释拉米夫定和流行的中草药制剂之间的草药相互作用提供了建设性信息。 (C) 2014 Elsevier B.V. 保留所有权利。
The aim of study is to develop a novel multiple microdialysis technique coupled to a validated chromatographic system for the measurement of protein-unbound form lamivudine and investigation of its herb-drug interaction in rat blood and liver. Furthermore, gene expression changes of drug metabolizing enzymes in rat were evaluated by microarray analysis after being treated with a traditional Chinese herbal formulation, Long-Dan-Xie-Gan-Tang (LDXGT). The analyte was separated by a reverse-phase C18 column using the mobile phase comprising methanol and 10 mM KH2PO4 (15:85, v/v, adjusted to pH 6.0 with NaOH) with the flow rate of 0.8 mL/min, and the UV wavelength was set at 270 nm. The processes of method validation followed Food and Drug Administration (FDA) guidelines. The pharmacokinetic data demonstrated that the area under the concentration-time curve (AUC) of the lamivudine alone and the LDXGT pretreated group were 532 +/- 37.6 and 550 +/- 44.2 min mu g/mL in rat blood after lamivudine administration (10 mg/kg, i.v.) and 682 +/- 196 and 642 +/- 153 min mu g/mL in rat liver, respectively. The herb-drug pharmacokinetic interaction showed that with either lamivudine alone or in combination with pretreated with LDXGT, the pharmacokinetic parameters were not significantly changed except the apparent volume of distribution (V-d) at a high dose of lamivudine (30 mg/kg). In addition, microarray analysis showed that among 70 altered genes (selection criteria: vertical bar Fold change vertical bar >= 2 and p < 0.05), only 11 genes were involved in drug metabolism and indicated that a relatively small portion of drug metabolizing genes in liver were altered at the genome level after the therapeutic dose of LDXGT treatment. In conclusion, these studies provide constructive information to interpret the herb-drug interactions between lamivudine and a popular Chinese herbal formulation. (C) 2014 Elsevier B.V. All rights reserved.