Pharmacokinetic interaction of diosmetin and silibinin with other drugs: Inhibition of CYP2C9-mediated biotransformation and displacement from serum albumin

Biomedicine and Pharmacotherapy

Volumn 102, Issue , 2018, Pages 912-921

  Poór, Miklós ^a   Boda, Gabriella ^a   Mohos, Violetta ^a   Kuzma, Mónika ^b   Bálint, Mónika ^b   Hetényi, Csaba ^b   Bencsik, Tímea ^a  

^a UNIVERSITY OF PÉCS   (Hungary)

^b UNIVERSITY OF PÉCS   (Hungary)

Author keywords

CYP2C9 inhibition; Diosmetin; Human serum albumin; Pharmacokinetic interaction; Silibinin; Warfarin

Indexed keywords

4' HYDROXYDICLOFENAC; BOVINE SERUM ALBUMIN; CYTOCHROME P450 2C9; DICLOFENAC; DIOSMETIN; HUMAN SERUM ALBUMIN; SERUM ALBUMIN; SILIBININ; UNCLASSIFIED DRUG; WARFARIN; CYTOCHROME P450 2C9 INHIBITOR; FLAVONOID; SILYMARIN;

ANISOTROPY; ARTICLE; BIOTRANSFORMATION; CONCENTRATION RESPONSE; DRUG METABOLISM; DRUG POTENCY; DRUG TRANSFORMATION; ENZYME INHIBITION; FLUORESCENCE SPECTROSCOPY; MOLECULAR MODEL; PRIORITY JOURNAL; ULTRAFILTRATION; CHEMISTRY; DRUG EFFECT; DRUG INTERACTION; HUMAN; KINETICS; METABOLISM; MOLECULAR DOCKING; SPECTROFLUOROMETRY; TIME FACTOR;

ANISOTROPY; BIOTRANSFORMATION; CYTOCHROME P-450 CYP2C9; CYTOCHROME P-450 CYP2C9 INHIBITORS; DICLOFENAC; DRUG INTERACTIONS; FLAVONOIDS; HUMANS; KINETICS; MOLECULAR DOCKING SIMULATION; SERUM ALBUMIN; SERUM ALBUMIN, BOVINE; SILYMARIN; SPECTROMETRY, FLUORESCENCE; TIME FACTORS; ULTRAFILTRATION; WARFARIN;

EID: 85044586759     PISSN: 07533322     EISSN: 19506007     Source Type: Journal    
DOI: 10.1016/j.biopha.2018.03.146     Document Type: Article

References (63)

1. Amato, C., Advantage of a micronized flavonoidic fraction (Daflon 500 mg) in comparison with a nonmicronized diosmin. Angiology 45 (1994), 531–536.
2. Savel'ev, V.S., Pokrovskii, A.V., Sapelkin, S.V., Bogachev, I.V., Bogdanets, I.L., Zolotukhin, I.A., Micronized diosmin (Detralex) for vein-related trophic ulcers: European experience. Angiol. Sosud. Khir. 12 (2006), 53–60.
3. Yang, Y., Gong, X.B., Huang, L.G., Wang, Z.X., Wan, R.Z., Zhang, P., Zhang, Q.Y., Chen, Z., Zhang, B.S., Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice. Oncotarget 8 (2017), 30723–30733.
4. Xu, Z., Yan, Y., Xiao, L., Dai, S., Zeng, S., Qian, L., Wang, L., Yang, X., Xiao, Y., Gong, Z., Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway. PLoS One, 12, 2017, e0175977.
5. Yang, K., Li, W.F., Yu, J.F., Yi, C., Huang, W.F., Diosmetin protects against ischemia/reperfusion-induced acute kidney injury in mice. J. Surg. Res. 214 (2017), 69–78.
6. Poór, M., Veres, B., Jakus, P.B., Antus, C., Montskó, G., Zrínyi, Z., Vladimir-Knežević, S., Petrik, J., Kőszegi, T., Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A. J. Photochem. Photobiol. B 132 (2014), 1–9.
7. Poór, M., Zrínyi, Z., Kőszegi, T., Structure related effects of flavonoid aglycones on cell cycle progression of HepG2 cells: metabolic activation of fisetin and quercetin by catechol-O-methyltransferase (COMT). Biomed. Pharmacother. 83 (2016), 998–1005.
8. Cova, D., De Angelis, L., Giavarini, F., Palladini, G., Perego, R., Pharmacokinetics and metabolism of oral diosmin in healthy volunteers. Int. J. Clin. Pharmacol. Ther. Toxicol. 30 (1992), 29–33.
9. Campanero, M.A., Escolar, M., Perez, G., Garcia-Quetglas, E., Sadaba, B., Azanza, J.R., Simultaneous determination of diosmin and diosmetin in human plasma by ion trap liquid chromatography–atmospheric pressure chemical ionization tandem mass spectrometry: application to a clinical pharmacokinetic study. J. Pharm. Biomed. Anal. 51 (2010), 875–881.
10. Tripoli, E., Guardia, M.La, Giammanco, S., Di Majo, D., Giammanco, M., Citrus flavonoids: molecular structure, biological activity and nutritional properties: a review. Food Chem. 104 (2007), 466–479.
11. Gattuso, G., Caristi, C., Gargiulli, C., Bellocco, E., Toscano, G., Leuzzi, U., Flavonoid glycosides in bergamot juice (Citrus bergamia Risso. J. Agric. Food Chem. 54 (2006), 3929–3935.
12. Meirinhos, J., Silva, B.M., Valentão, P., Seabra, R.M., Pereira, J.A., Dias, A., Andrade, P.B., Ferreres, F., Analysis and quantification of flavonoidic compounds from Portuguese olive (Olea europaea L.) leaf cultivars. Nat. Prod. Res. 19 (2005), 189–195.
13. Fraschini, F., Demartini, G., Esposti, D., Pharmacology of silymarin. Clin. Drug Invest. 22 (2002), 51–65.
14. Federico, A., Dallio, M., Loguercio, C., Silymarin/silybin and chronic liver disease: a marriage of many years. Molecules, 22, 2017, 191.
15. Neha, A.S., Jaggi, N., Singh, Silymarin and its role in chronic diseases. Adv. Exp. Med. Biol. 929 (2016), 25–44.
16. Stolf, A.M., Cardoso, C.C., Acco, A., Effects of silymarin on diabetes mellitus complications: a review. Phytother. Res. 31 (2017), 366–374.
17. Tan, Z.R., Zhou, Y.X., Liu, J., Huang, W.H., Chen, Y., Wang, Y.C., Wang, L.S., The influence of ABCB1 polymorphism C3435T on the pharmacokinetics of silibinin. J. Clin. Pharm. Ther. 40 (2015), 685–688.
18. Lorenz, D., Lücker, P.W., Mennicke, W.H., Wetzelsberger, N., Pharmacokinetic studies with silymarin in human serum and bile. Methods Find. Exp. Clin. Pharmacol. 6 (1984), 655–661.
19. Schmidt, S., Gonzalez, D., Derendorf, H., Significance of protein binding in pharmacokinetics and pharmacodynamics. J. Pharm. Sci. 99 (2010), 1107–1122.
20. Fanali, G., Di Masi, A., Trezza, V., Marino, M., Fasano, M., Ascenzi, P., Human serum albumin: from bench to bedside. Mol. Asp. Med. 33 (2012), 209–290.
21. Zhang, G., Wang, L., Pan, J., Probing the binding of the flavonoid diosmetin to human serum albumin by multispectroscopic techniques. J. Agric. Food Chem. 60 (2012), 2721–2729.
22. Maiti, T.K., Ghosh, K.S., Samanta, A., Dasgupta, S., The interaction of silibinin with human serum albumin: a spectroscopic investigation. J. Photochem. Photobiol. A 194 (2008), 297–307.
23. Yamasaki, K., Sato, H., Minagoshi, S., Kyubun, K., Anraku, M., Miyamura, S., Watanabe, H., Taguchi, K., Seo, H., Maruyama, T., Otagiri, M., The binding of silibinin, the main constituent of silymarin, to site I on human serum albumin. Biol. Pharm. Bull. 40 (2017), 310–317.
24. Jarrar, Y.B., Lee, S.J., Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy. Drug. Metabol. Drug. Interact. 29 (2014), 211–220.
25. Quintieri, L., Bortolozzo, S., Stragliotto, S., Moro, S., Pavanetto, M., Nassi, A., Palatini, P., Floreani, M., Flavonoids diosmetin and hesperetin are potent inhibitors of cytochrome P450 2C9-mediated drug metabolism in vitro. Drug Metab. Pharmacokinet. 25 (2010), 466–476.
26. Chen, J.J., Zhang, J.X., Zhang, X.Q., Qi, M.J., Shi, M.Z., Yang, J., Zhang, K.Z., Guo, C., Han, Y.L., Effects of diosmetin on nine cytochrome P450 isoforms, UGTs and three drug transporters in vitro. Toxicol. Appl. Pharmacol. 334 (2017), 1–7.
27. Doehmer, J., Weiss, G., McGregor, G.P., Appel, K., Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol. In Vitro 25 (2011), 21–27.
28. Doehmer, J., Tewes, B., Klein, K.U., Gritzko, K., Muschick, H., Mengs, U., Assessment of drug-drug interaction for silymarin. Toxicol. In Vitro 22 (2008), 610–617.
29. Beckmann-Knopp, S., Rietbrock, S., Weyhenmeyer, R., Böcker, R.H., Beckurts, K.T., Lang, W., Hunz, M., Fuhr, U., Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol. Toxicol. 86 (2000), 250–256.
30. Sridar, C., Goosen, T.C., Kent, U.M., Williams, J.A., Hollenberg, P.F., Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab. Dispos. 32 (2004), 587–594.
31. Jancová, P., Anzenbacherová, E., Papousková, B., Lemr, K., Luzná, P., Veinlichová, A., Anzenbacher, P., Simánek, V., Silybin is metabolized by cytochrome P450 2C8 in vitro. Drug Metab. Dispos. 35 (2007), 2035–2039.
32. Brantley, S.J., Oberlies, N.H., Kroll, D.J., Paine, M.F., Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J. Pharmacol. Exp. Ther. 332 (2010), 1081–1087.
33. Rajnarayana, K., Venkatesham, A., Krishna, D.R., Bioavailability of diclofenac sodium after pretreatment with diosmin in healthy volunteers. Drug Metabol. Drug Interact. 22 (2007), 165–174.
34. Kumar, R.M., Van Gompel, J.J., Bower, R., Rabinstein, A.A., Spontaneous intraventricular hemorrhage associated with prolonged diosmin therapy. Neurocrit. Care 14 (2011), 438–440.
35. Kim, C.S., Choi, S.J., Park, C.Y., Li, C., Choi, J.S., Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats. Anticancer Res. 30 (2010), 79–85.
36. Lee, C.K., Choi, J.S., Effects of silibinin on the pharmacokinetics of carvedilol after oral administration in rats. J. Pharm. Invest. 41 (2011), 153–159.
37. Han, Y., Guo, D., Chen, Y., Chen, Y., Tan, Z.R., Zhou, H.H., Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur. J. Clin. Pharmacol. 65 (2009), 585–591.
38. Holford, N.H., Clinical pharmacokinetics and pharmacodynamics of warfarin. Understanding the dose-effect relationship. Clin. Pharmacokinet. 11 (1986), 483–504.
39. Chan, E., McLachlan, A.J., Pegg, M., MacKay, A.D., Cole, R.B., Rowland, M., Disposition of warfarin enantiomers and metabolites in patients during multiple dosing with rac-warfarin. Br. J. Clin. Pharmacol. 37 (1994), 563–569.
40. Chan, T.Y., Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: mechanisms, clinical significance, and avoidance. Ann. Pharmacother. 29 (1995), 1274–1283.
41. Holbrook, A.M., Pereira, J.A., Labiris, R., McDonald, H., Douketis, J.D., Crowther, M., Wells, P.S., Systematic overview of warfarin and its drug and food interactions. Arch. Intern. Med. 165 (2005), 1095–1106.
42. Di Bari, L., Ripoli, S., Pradhan, S., Salvadori, P., Interactions between quercetin and warfarin for albumin binding: a new eye on food/drug interference. Chirality 22 (2010), 593–596.
43. Poór, M., Li, Y., Kunsági-Máté, S., Petrik, J., Vladimir-Knežević, S., Kőszegi, T., Molecular displacement of warfarin from human serum albumin by flavonoid aglycones. J. Lumin. 142 (2013), 122–127.
44. Flora, D.R., Rettie, A.E., Brundage, R.C., Tracy, T.S., CYP2C9 genotype-dependent warfarin pharmacokinetics: impact of CYP2C9 genotype on R- and S-warfarin and their oxidative metabolites. J. Clin. Pharmacol. 57 (2017), 382–393.
45. Poór, M., Boda, G., Needs, P.W., Kroon, P.A., Lemli, B., Bencsik, T., Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed. Pharmacother. 88 (2017), 574–581.
46. Poór, M., Bálint, M., Hetényi, C., Gődér, B., Kunsági-Máté, S., Kőszegi, T., Lemli, B., Investigation of non-covalent interactions of aflatoxins (B1, B2, G1, G2, and M1) with serum albumin. Toxins, 9, 2017, 339.
47. Poór, M., Boda, G., Kunsági-Máté, S., Needs, P.W., Kroon, P.A., Lemli, B., Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3′-sulfate with different albumins. J. Lumin. 194 (2018), 156–163.
48. Poór, M., Lemli, B., Bálint, M., Hetényi, C., Sali, N., Kőszegi, T., Kunsági-Máté, S., Interaction of citrinin with human serum albumin. Toxins 7 (2015), 5155–5166.
49. Poór, M., Kunsági-Máté, S., Bálint, M., Hetényi, C., Gerner, Z., Lemli, B., Interaction of mycotoxin zearalenone with human serum albumin. J. Photochem. Photobiol. B 170 (2017), 16–24.
50. Lomonaco, T., Ghimenti, S., Piga, I., Onor, M., Melai, B., Fuoco, R., Francesco, F.Di, Determination of total and unbound warfarin and warfarin alcohols in human plasma by high performance liquid chromatography with fluorescence detection. J. Chromatogr. A 1314 (2013), 54–62.
51. Schrödinger Release 2017-4: Maestro. 2017, Schrödinger, LLC, New York, NY.
52. Stewart, J.J., MOPAC: a semiempirical molecular orbital program. J. Comput. Aided Mol. Des. 4 (1990), 1–105.
53. Stewart, J.J., Optimization of parameters for semiempirical methods V: modification of NDDO approximations and application to 70 elements. J. Mol. Model. 13 (2007), 1173–1213.
54. Abraham, M.J., Murtola, T., Schulz, R., Páll, S., Smith, J.C., Hess, B., Lindahl, E., GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2 (2015), 19–25.
55. Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J.L., Dror, R.O., Shaw, D.E., Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 78 (2010), 1950–1958.
56. Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J., AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30 (2009), 2785–2791.
57. Hetényi, C., van der Spoel, D., Efficient docking of peptides to proteins without prior knowledge of the binding site. Protein Sci. 11 (2002), 1729–1737.
58. Hetényi, C., van der Spoel, D., Blind docking of drug-sized compounds to proteins with up to a thousand residues. FEBS Lett. 580 (2006), 1447–1450.
59. Hetényi, C., van der Spoel, D., Toward prediction of functional protein pockets using blind docking and pocket search algorithms. Protein Sci. 20 (2011), 880–893.
60. Brantley, S.J., Gufford, B.T., Dua, R., Fediuk, D.J., Graf, T.N., Scarlett, Y.V., Frederick, K.S., Fisher, M.B., Oberlies, N.H., Paine, M.F., Physiologically based pharmacokinetic modeling framework for quantitative prediction of an herb-drug interaction. CPT Pharmacomet. Syst. Pharmacol., 3, 2014, e107.
61. Rimac, H., Dufour, C., Debeljak, Ž., Zorc, B., Bojić, M., Warfarin and flavonoids do not share the same binding region in binding to the IIA subdomain of human serum albumin. Molecules, 22, 2017, 1153.
62. Yamasaki, K., Maruyama, T., Takadate, A., Suenaga, A., Kragh-Hansen, U., Otagiri, M., Characterization of site I of human serum albumin using spectroscopic analyses: locational relations between regions Ib and Ic of site I. J. Pharm. Sci. 93 (2004), 3004–3012.
63. Chen, Y.C., Wang, H.M., Niu, Q.X., Ye, D.Y., Liang, G.W., Binding between saikosaponin C and human serum albumin by fluorescence spectroscopy and molecular docking. Molecules, 21, 2016, 153.