Open Access

Impact of quercetin‑induced changes in drug‑metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats

  • Authors:
    • Yani Liu
    • Xiaomei Luo
    • Chunxiao Yang
    • Tingyu Yang
    • Jiali Zhou
    • Shaojun Shi
  • View Affiliations

  • Published online on: August 9, 2016     https://doi.org/10.3892/mmr.2016.5616
  • Pages: 3073-3085
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to evaluate whether quercetin (Que) modulates the mRNA and protein expression levels of drug‑metabolizing enzymes (DMEs) and drug transporters (DTs) in the small intestine and liver, and thus modifies the pharmacokinetic profile of cyclosporine (CsA) in rats. This two‑part study evaluated the pharmacokinetic profiles of CsA in the presence or absence of Que (experiment I) and the involvement of DMEs and DTs (experiment II). In experiment I, 24 rats received single‑dose CsA (10 mg/kg) on day 1, single‑dose Que (25, 50 and 100 mg/kg/day; eight rats in each group) on days 3‑8, and concomitant CsA/Que on day 9. In experiment II, the mRNA and protein expression levels of cytochrome P (CYP)3A1, CYP3A2, UDP glucuronosyltransferase family 1 member A complex locus, organic anion‑transporting polypeptide (OATP)2B1, OATP1B2, P‑glycoprotein, breast cancer resistance protein, and multidrug resistance‑associated protein 2 in the small intestine and liver of rats were analyzed following oral administration of Que at 25, 50 and 100 mg/kg in the presence or absence of CsA (10 mg/kg) for seven consecutive days. Co‑administration of Que (25,50 and 100 mg/kg) decreased the maximum serum concentration of CsA by 46, 50 and 47% in a dose‑independent manner. In addition, the area under the curve to the last measurable concentration and area under the curve to infinite time were decreased, by 21 and 16%, 30 and 33%, and 33 and 34% (P<0.01), respectively. However, the mRNA and protein expression levels of the above‑mentioned DMEs and DTs were inhibited by Que in a dose‑dependent manner (P<0.01) to a similar extent in the small intestine and liver. It was demonstrated that Que was able to reduce the bioavailability of CsA following multiple concomitant doses in rats. Overlapping modulation of intestinal and hepatic DMEs and DTs, as well as the DME‑DT interplay are potential explanations for these observations.
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October-2016
Volume 14 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Liu Y, Luo X, Yang C, Yang T, Zhou J and Shi S: Impact of quercetin‑induced changes in drug‑metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats. Mol Med Rep 14: 3073-3085, 2016
APA
Liu, Y., Luo, X., Yang, C., Yang, T., Zhou, J., & Shi, S. (2016). Impact of quercetin‑induced changes in drug‑metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats. Molecular Medicine Reports, 14, 3073-3085. https://doi.org/10.3892/mmr.2016.5616
MLA
Liu, Y., Luo, X., Yang, C., Yang, T., Zhou, J., Shi, S."Impact of quercetin‑induced changes in drug‑metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats". Molecular Medicine Reports 14.4 (2016): 3073-3085.
Chicago
Liu, Y., Luo, X., Yang, C., Yang, T., Zhou, J., Shi, S."Impact of quercetin‑induced changes in drug‑metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats". Molecular Medicine Reports 14, no. 4 (2016): 3073-3085. https://doi.org/10.3892/mmr.2016.5616