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In vivo distribution and pharmacokinetics of multiple active components from Danshen and Sanqi and their combination via inner ear administration

Authors Long, Wei; Zhang, Shi-Chang; Wen, Lu; Mu, Lei; Yang, Fan; Chen, Gang

Journal JOURNAL OF ETHNOPHARMACOLOGY , OCT 28 2014,:156

DOI 10.1016/j.jep.2014.08.041 PubMed 25218322

Abstract 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.

Species covered 丹参 Salvia miltiorrhiza 头花香薷 Elsholtzia capituligera