Kammalla Ananth Kumar, Ramasamy Mohan Kumar, Chintala Jyothi, Dubey Govind Prasad, Agrawal Aruna, Kaliappan Ilango
Interdisciplinary School of Indian System of Medicine (ISISM), SRM University, Kattankulathur, Kancheepuram (Dt), 603203, Tamil Nadu, India.
Eur J Drug Metab Pharmacokinet. 2015 Sep;40(3):277-84. doi: 10.1007/s13318-014-0206-9. Epub 2014 Jun 3.
Quercetin and Rutin are most common flavone constituents of some herb extracts such as Hippophae rhamnoides L. Inter and intra herb pharmacokinetics interactions of Quercetin and Rutin were investigated in the present study. Pharmacokinetic study was investigated in the two groups of rats (n = 6) for pharmacokinetic interactions between the Quercetin and Rutin (2.5 mg/kg) mixture treated alone with European patented polyherbal formulation containing equivalent weight of the above. The total plasma concentrations of Quercetin and Rutin were determined by liquid chromatography mass spectrometry (LC-MS). A method was developed and validated according to the ICH guidelines. The results of the present study shows that there are great differences in the pharmacokinetics of Quercetin and Rutin when they are administered together and from the polyherbal formulation which will be interacted by many other constituents. The bioavailability of Quercetin was lowered from the polyherbal formulation when compared with the co-administration, whereas the Rutin bioavailability has increased from the polyherbal formulation when compared with the co-administration. The maximum plasma concentration of Quercetin from coadministration and polyherbal formulation was 165.3 ± 31.9 and 90.8 ± 21.4 ng/mL, respectively, whereas in the case of Rutin it was 61.1 ± 29.3 and 121.7 ± 19.2 ng/mL. After polyherbal formulation administration to rats the AUC0-24, AUC0-∞ and AUMC0-∞ of both Quercetin and Rutin significantly increased when compared to co-administration. The above results proved that inter and intra herb pharmacokinetic interactions between Quercetin and Rutin. Possible interactions of the other constituents with hydrolyzing enzymes in the formulation enhances the oral bioavailability of Rutin. Accordingly besides the drug herb interactions, inter and intra herb interaction might be brought into view with the wide use of herbal remedies.
槲皮素和芦丁是一些草药提取物(如沙棘)中最常见的黄酮成分。本研究对槲皮素和芦丁的草药内和草药间药代动力学相互作用进行了研究。在两组大鼠(n = 6)中进行了药代动力学研究,以考察单独给予槲皮素和芦丁(2.5 mg/kg)混合物以及给予含有同等重量上述成分的欧洲专利复方草药制剂时的药代动力学相互作用。通过液相色谱-质谱联用(LC-MS)测定槲皮素和芦丁的总血浆浓度。根据国际人用药品注册技术协调会(ICH)指南开发并验证了一种方法。本研究结果表明,槲皮素和芦丁一起给药时以及从复方草药制剂给药时,其药代动力学存在很大差异,复方草药制剂会与许多其他成分发生相互作用。与联合给药相比,复方草药制剂使槲皮素的生物利用度降低,而芦丁的生物利用度则有所提高。联合给药和复方草药制剂给药时,槲皮素的最大血浆浓度分别为165.3±31.9和90.8±21.4 ng/mL,而芦丁的最大血浆浓度分别为61.1±29.3和121.7±19.2 ng/mL。给大鼠给予复方草药制剂后,与联合给药相比,槲皮素和芦丁的AUC0-24、AUC0-∞和AUMC0-∞均显著增加。上述结果证明了槲皮素和芦丁之间存在草药内和草药间药代动力学相互作用。制剂中其他成分与水解酶的可能相互作用提高了芦丁的口服生物利用度。因此,除了药物与草药的相互作用外,随着草药疗法的广泛应用,草药内和草药间的相互作用也可能值得关注。