In vivo distribution and pharmacokinetics of multiple active components from Danshen and Sanqi and their combination via inner ear administration
In vivo distribution and pharmacokinetics of multiple active components from Danshen and Sanqi and their combination via inner ear administration
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丹参、三七及其内耳给药组合多种活性成分的体内分布和药代动力学
DOI：
10.1016/j.jep.2014.08.041
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发表时间：
2014-10-28
影响因子：
5.4
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Long, Wei;Zhang, Shi-Chang;Chen, Gang
民族药理学相关性：丹参和三七（Burk.）陈凤花（五缘科植物，中文名三七）在中医治疗冠心病、脑血管病和内耳疾患方面有着悠久的历史。为了给临床提供合理的用药依据，我们通过静脉给药和内耳给药，考察了标记物在丹参和三七的体内分布和药代动力学，并探讨了这些标记物在复方中的潜在相互作用。材料与方法：分别给予丹参提取物（丹酚酸B）、丹参酮三七提取物（三七皂苷）及两种提取物联合静脉和鼓内给药（IT）。在不同时间点采集脑、内耳淋巴周围、脑脊液和血浆标本。采用高效液相色谱-二极管阵列检测器（DAD）法测定丹参酚酸B （Sal B）、丹参酮IIA （Ts IIA）、三七皂苷R-1 （R-1）、人参皂苷Rg(1) （Rg(1)）和人参皂苷Rb-1 （Rb-1）的浓度。采用非区室法估计药代动力学参数。结果：与静脉给药相比，经内耳局部给药可显著改善药物在左心室、脑脊液和脑组织内的分布。经IT处理后的C-max和AUC（(0-t)）值均显著高于IV。复方中R-1、Rg(1)、Rb-1、Sal B、Ts IIA的药动学参数与单用丹参、三七的药动学参数比较差异有统计学意义。复方配伍增强了丹参成分经内耳进入脑内的转运，明显延长了丹参成分在脑脊液中的滞留时间，同时降低了三七成分在内耳和脑内的分布。结论：内耳局部给药比全身给药更有效。丹参和三七合用可引起豚鼠体内显著的药代动力学相互作用。经内耳给药的多重活性成分可能是治疗内耳和脑部疾病的有希望的候选者。2014爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Salvia miltiorrhiza Bunge (Labiatae sp. plant, Chinese name Danshen) and Panax notoginseng (Burk.) F. H. Chen (Araliaceae plant, Chinese name Sanqi) have a long history in treating coronary heart disease, cerebrovascular disease and inner ear disorders in traditional Chinese medicine. To provide a rational basis for the use of these herbs in clinical practice, we investigated the in vivo distribution and pharmacokinetics of marker agents in Danshen and Sanqi via intravenous and inner ear administration and explored the potential interactions of these agents in compound prescription.Materials and methods: Guinea pigs were given Danshen extracts (salvianolic acid B, tanshinone Sanqi extracts (Panax notoginseng saponins) and combination of the two extracts via intravenous and intratympanic administration (IT). Samples from the brain, inner ear perilymph (PL), cerebrospinal fluid (CSF) and plasma were collected at different time points. The concentration of salvianolic acid B (Sal B), tanshinone IIA (Ts IIA), notoginsenoside R-1 (R-1), ginsenoside Rg(1) (Rg(1)) and ginsenoside Rb-1 (Rb-1) was determined by high-performance liquid chromatography coupled with a diode array detector (DAD). Pharmacokinetic parameters were estimated using non-compartmental methods.Results: Local drug application via inner ear greatly improved drug distribution within the PL, CSF and brain tissues compared with intravenous administration (IV). The values of C-max and AUC((0-t)) after IT were significantly higher than IV. In comparison with IT of Danshen and Sanqi alone, the pharmacokinetic parameters for R-1, Rg(1), Rb-1, Sal B and Ts IIA were markedly different in the compound prescription. The compound compatibility enhanced the transport of Danshen components into the brain through the inner ear and apparently prolonged the retention time in CSF while decreasing the distribution of Sanqi components in the inner ear and brain.Conclusions: The results indicated that local drug application to the inner ear was a more effective delivery route than systemic administration. Co-administration of Danshen and Sanqi could cause significant pharmacokinetic herb-herb interactions in guinea pigs. The multiple active components via inner ear administration might be promising candidates for the treatment of inner ear and brain diseases. (C) 2014 Elsevier Ireland Ltd. All rights reserved.