Comparative pharmacokinetic interactions of Quercetin and Rutin in rats after oral administration of European patented formulation containing Hipphophae rhamnoides and Co-administration of Quercetin and Rutin

Abstract

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.

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

“…To our knowledge, no published data are available related to the in vivo effects of NADES as administration tools for bioactive constituents. These eutectics, prepared using different starting materials, can be divided into five groups, the first is based on urea (1-4), the second on polyalcohols and sugars (5-6), the third on organic acid and sugars (7)(8)(9), the fourth on organic acid and amino acid (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and the fifth group was prepared using choline chloride, sugars and amino acid (28)(29)(30). Our results show the ability of various NADES to dissolve rutin.…”

“…Considering the solubility properties nine NADES (2,3,4,10,11,17,28,29,30) were able to solubilize half of the rutin compared to the best solvent (ethanol). On the other hand, eutectic 11 and 28 (proline/glutamic acid 2:1 and proline/choline chloride 1:2 respectively) resulted to be the most promising NADES presenting rutin solubilization higher than ethanol and methanol.…”

“…Additionally, there are two pharmacokinetic studies with oral administration of rutin in rats. Recently, rutin and quercetin as patented polyherbal formulations were co-administered in rats by gavage, and bioavailability was compared to that of the co-administration of the two pure compounds at equivalent doses [29]. The observed differences indicated that from the polyherbal formulation bioavailability of rutin had increased, while bioavailability of quercetin has decreased when compared to the co-administration [29].…”

“…Recently, rutin and quercetin as patented polyherbal formulations were co-administered in rats by gavage, and bioavailability was compared to that of the co-administration of the two pure compounds at equivalent doses [29]. The observed differences indicated that from the polyherbal formulation bioavailability of rutin had increased, while bioavailability of quercetin has decreased when compared to the co-administration [29]. In a methodological paper describing an HPLC-MS/MS method for rutin quantification in rat plasma, preliminary pharmacokinetic data were published showing the maximum concentration (1659 ng/mL) 5 min after 2.5 mg/kg sublingual vein administration of rutin [28].…”

Enhancement of flavonoid ability to cross the blood–brain barrier of rats by co-administration with α-tocopherol

“…25 Recently the co-administration of quercetin and rutin has led to an enhancement of plasmatic quercetin bioavailability in rats. 27 Despite the numerous studies supporting the neuroprotective activity of flavonoids, the main issue to be elucidated concerns the ability of flavonoids to cross the BBB [28][29][30] and the interactions among the co-administered molecules. 31 This study was aimed to evaluate the plasma bioavailability of EGCG, quercetin and rutin ( Fig.…”