Skip to content
2000
Volume 12, Issue 1
  • ISSN: 2215-0838
  • E-ISSN: 2215-0846

Abstract

Background

Sildenafil is a drug that belongs to the group of phosphodiesterase-5 inhibitors. It is used in the treatment of erectile dysfunction and pulmonary arterial hypertension. Sildenafil undergoes metabolism in the liver by CYP3A4 and CYP2C9. Therefore, drug interactions may occur if sildenafil is taken simultaneously with CYP3A4 and CYP2C9 inhibitors such as green tea catechins.

Objective

The aim of the present work was to analyze epigallocatechin-3-gallate (EGCG) and caffeine content in total extract and catechin fraction from Bancha green tea leaves as well as to assess their effect on sildenafil pharmacokinetics in rats.

Methods

Animals received sildenafil alone and in combination with total Bancha green tea extract, catechin fraction or ketoconazole (a well-known CYP3A4 inhibitor). The plant extracts and the plasma concentrations of sildenafil were analyzed with high-performance liquid chromatography.

Results

Administration of sildenafil after pretreatment of the rats with total extract and catechin fraction from Bancha green tea resulted in a statistically significant increase in C, AUC and AUC and a decrease in the volume of distribution and clearance of sildenafil compared to the control group. A significant increase in C, AUC and AUC of sildenafil was also observed after simultaneous intake of sildenafil and ketoconazole.

Conclusion

Co-administration of sildenafil and the isolated Bancha green tea extracts led to a significant change in sildenafil pharmacokinetics in rats. Therefore, further, studies are necessary to clarify the exact mechanisms responsible for the interactions established as well as to evaluate the risk for clinically significant interactions in humans.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/ctm/10.2174/0122150838305894240724112703
2024-07-31
2025-11-12
Loading full text...

Full text loading...

/deliver/fulltext/ctm/12/1/CTM-12-E310724232511.html?itemId=/content/journals/ctm/10.2174/0122150838305894240724112703&mimeType=html&fmt=ahah

References

  1. PrasanthM. SivamaruthiB. ChaiyasutC. TencomnaoT. A review of the role of Green tea (Camellia sinensis) in antiphotoaging, stress resistance, neuroprotection, and autophagy.Nutrients201911247410.3390/nu1102047430813433
    [Google Scholar]
  2. TruongV.L. JeongW.S. Cellular defensive mechanisms of tea polyphenols: Structure-activity relationship.Int. J. Mol. Sci.20212217910910.3390/ijms2217910934502017
    [Google Scholar]
  3. TangG.Y. MengX. GanR.Y. Health functions and related molecular mechanisms of tea components: An update review.Int. J. Mol. Sci.20192024619610.3390/ijms2024619631817990
    [Google Scholar]
  4. XingL. ZhangH. QiR. TsaoR. MineY. Recent advances in the understanding of the health benefits and molecular mechanisms associated with Green tea polyphenols.J. Agric. Food Chem.20196741029104310.1021/acs.jafc.8b0614630653316
    [Google Scholar]
  5. BagS. MondalA. MajumderA. BanikA. Tea and its phytochemicals: Hidden health benefits & modulation of signaling cascade by phytochemicals.Food Chem.202237113109810.1016/j.foodchem.2021.13109834634647
    [Google Scholar]
  6. KhanN. MukhtarH. Tea polyphenols in promotion of human health.Nutrients20181113910.3390/nu1101003930585192
    [Google Scholar]
  7. LIczbiński P Bukowska B. Tea and coffee polyphenols and their biological properties based on the latest in vitro investigations.Ind. Crops Prod.202217511426510.1016/j.indcrop.2021.11426534815622
    [Google Scholar]
  8. SanchezJ. Methylxanthine content in commonly consumed foods in Spain and determination of its intake during consumption.Foods201761210910.3390/foods612010929207513
    [Google Scholar]
  9. NehligA. Interindividual differences in caffeine metabolism and factors driving caffeine consumption.Pharmacol. Rev.201870238441110.1124/pr.117.01440729514871
    [Google Scholar]
  10. KraheJ. KraheM.A. NaumovskiN. The implications of post-harvest storage time and temperature on the phytochemical composition and quality of japanese-styled Green tea grown in australia: A food loss and waste recovery opportunity.Beverages2021722510.3390/beverages7020025
    [Google Scholar]
  11. WakamatsuM. YamanouchiH. SaharaH. Catechin and caffeine contents in green tea at different harvest periods and their metabolism in miniature swine.Food Sci. Nutr.2019782769277810.1002/fsn3.114331428365
    [Google Scholar]
  12. CandelaL. FormatoM. CrescenteG. PiccolellaS. PacificoS. Coumaroyl flavonol glycosides and more in marketed Green teas: An intrinsic value beyond much-lauded catechins.Molecules2020258176510.3390/molecules2508176532290396
    [Google Scholar]
  13. KochW. Kukula-KochW. KomstaŁ. MarzecZ. SzwercW. GłowniakK. Green tea quality evaluation based on its catechins and metals composition in combination with chemometric analysis.Molecules2018237168910.3390/molecules2307168929997337
    [Google Scholar]
  14. MakiuchiT. SobueT. KitamuraT. Association between green tea/coffee consumption and biliary tract cancer: A population‐based cohort study in Japan.Cancer Sci.20161071768310.1111/cas.1284326530716
    [Google Scholar]
  15. Burana-osotJ. YanpaisanW. Catechins and caffeine contents of green tea commercialized in Thailand.J. Pharm. Biomed. Sci.2012222217
    [Google Scholar]
  16. MusialC. Kuban-JankowskaA. Gorska-PonikowskaM. Beneficial properties of Green tea catechins.Int. J. Mol. Sci.2020215174410.3390/ijms2105174432143309
    [Google Scholar]
  17. WerbaJ.P. MisakaS. GiroliM.G. Update of green tea interactions with cardiovascular drugs and putative mechanisms.J Food Drug Anal 2018262S72S7710.1016/j.jfda.2018.01.00829703388
    [Google Scholar]
  18. AlbassamA. MarkowitzJ. An appraisal of drug-drug interactions with Green tea (Camellia sinensis).Planta Med.201783649650810.1055/s‑0043‑10093428118673
    [Google Scholar]
  19. IvanyukA. LivioF. BiollazJ. BuclinT. Renal drug transporters and drug interactions.Clin. Pharmacokinet.201756882589210.1007/s40262‑017‑0506‑828210973
    [Google Scholar]
  20. KnopJ. MisakaS. SingerK. Inhibitory effects of Green tea and (-)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein.PLoS One20151010e013937010.1371/journal.pone.013937026426900
    [Google Scholar]
  21. ObaidatA. RothM. HagenbuchB. The expression and function of organic anion transporting polypeptides in normal tissues and in cancer.Annu. Rev. Pharmacol. Toxicol.201252113515110.1146/annurev‑pharmtox‑010510‑10055621854228
    [Google Scholar]
  22. SchollC. LepperA. LehrT. Population nutrikinetics of green tea extract.PLoS One2018132e019307410.1371/journal.pone.019307429466429
    [Google Scholar]
  23. AnderssonK-E. PDE5 inhibitors – pharmacology and clinical applications 20 years after sildenafil discovery.Br. J. Pharmacol.2018175132554256510.1111/bph.1420529667180
    [Google Scholar]
  24. AtsbehaB.W. KebedeB.T. BirhanuB.S. YimenuD.K. BelayW.S. DemekeC.A. The weekend drug; Recreational use of sildenafil citrate and concomitant factors: A cross-sectional study.Front. Med.2021866524710.3389/fmed.2021.66524734490285
    [Google Scholar]
  25. AbdelkawyK.S. DoniaA.M. TurnerR.B. ElbarbryF. Effects of lemon and seville orange juices on the pharmacokinetic properties of sildenafil in healthy subjects.Drugs R D.201616327127810.1007/s40268‑016‑0140‑127550653
    [Google Scholar]
  26. MirandaC. Pérez-RodríguezZ. Hernández-ArmengolR. Quiñones-GarcíaY. Betancourt-PurónT. Cabrera-PérezM.Á. Biowaiver or bioequivalence: Ambiguity in sildenafil citrate BCS classification.AAPS PharmSciTech20181941693169810.1208/s12249‑018‑0982‑729532425
    [Google Scholar]
  27. ChoiM.K. SongI.S. Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil.J. Pharm. Pharmacol.20126481074108310.1111/j.2042‑7158.2012.01498.x22775210
    [Google Scholar]
  28. HigashiH. WatanabeN. TamuraR. TaguchiM. In vitro P-glycoprotein-mediated transport of tadalafil: A comparison with sildenafil.Biol. Pharm. Bull.20174081314131910.1248/bpb.b17‑0027828769012
    [Google Scholar]
  29. PengY. ChengZ. XieF. Evaluation of pharmacokinetic drug-drug interactions: A review of the mechanisms, in vitro and in silico approaches.Metabolites20211127510.3390/metabo1102007533513941
    [Google Scholar]
  30. DhaliwalA. GuptaM. PDE5 inhibitors.In:StatPearls.Treasure Island, FLStatPearls Publishing2022
    [Google Scholar]
  31. MallahE. WalidS. RayyanW. Dose-dependent synergistic effect of Pomegranate juice on the bioavailability of sildenafil in rats by using HPLC method.Lat. Am. J. Pharm.201635612771284
    [Google Scholar]
  32. KatzA. EfrosM. KaminetskyJ. HerrlingerK. ChirouzesD. CeddiaM. A green and black tea extract benefits urological health in men with lower urinary tract symptoms.Ther. Adv. Urol.201463899610.1177/175628721452692424883106
    [Google Scholar]
  33. RatnasooriyaW.D. FernandoT.S.P. Effect of black tea brew of Camellia sinensis on sexual competence of male rats.J. Ethnopharmacol.2008118337337710.1016/j.jep.2008.04.02318565706
    [Google Scholar]
  34. DuralE. Investigation of the presence of sildenafil in herbal dietary supplements by validated HPLC method.Turk J Pharm Sci2020171566210.4274/tjps.galenos.2018.9124932454761
    [Google Scholar]
  35. MoserD. HussainS. YaqoobM. RainerM. JakschitzT. BonnG.K. Fast and semiquantitative screening for sildenafil in herbal over-the-counter formulations with atmospheric pressure solid analysis probe (ASAP) to prevent medicinal adulteration.J. Pharm. Biomed. Anal.202221411472010.1016/j.jpba.2022.11472035286987
    [Google Scholar]
  36. LinL. QuF. NieP. ZhangH. ChuB. HeY. Rapid and quantitative determination of sildenafil in cocktail based on surface enhanced raman spectroscopy.Molecules2019249179010.3390/molecules2409179031075815
    [Google Scholar]
  37. XiaoS. HeY. Analysis of sildenafil in liquor and health wine using surface enhanced raman spectroscopy.Int. J. Mol. Sci.20192011272210.3390/ijms20112722
    [Google Scholar]
  38. OuranidisA. TsiaxerliA. VardakaE. Sildenafil 4.0-integrated synthetic chemistry, formulation and analytical strategies effecting immense therapeutic and societal impact in the fourth industrial era.Pharmaceuticals202114436510.3390/ph1404036533920975
    [Google Scholar]
  39. SocałaK. NieoczymD. WyskaE. WlaźP. Effect of sildenafil on the activity of some antidepressant drugs and electroconvulsive shock treatment in the forced swim test in mice.Naunyn Schmiedebergs Arch. Pharmacol.2017390433934910.1007/s00210‑016‑1334‑328013355
    [Google Scholar]
  40. StoevaS. Radeva-IlievaM. ZhelevI. GeorgievK. A HPLC-UV method for analysis of total plant extract and catechin fraction of Bancha green tea.Nat. Prod. J.2023132e12052220470310.2174/2210315512666220512212448
    [Google Scholar]
  41. Radeva-llievaM. StoevaS. HvarchanovaN. ZhelevI. GeorgievK.D. Influence of methylxanthines isolated from Bancha green tea on the pharmacokinetics of sildenafil in rats.Daru2022301758410.1007/s40199‑022‑00433‑z35146639
    [Google Scholar]
  42. Mauvais-JarvisF. ArnoldA.P. ReueK. A guide for the design of pre-clinical studies on sex differences in metabolism.Cell Metab.20172561216123010.1016/j.cmet.2017.04.03328591630
    [Google Scholar]
  43. BelaynehA. MollaF. The effect of coffee on pharmacokinetic properties of drugs: A review.BioMed Res. Int.2020202011110.1155/2020/790970332775441
    [Google Scholar]
  44. HeimannM. KäsermannH.P. PfisterR. RothD.R. BürkiK. Blood collection from the sublingual vein in mice and hamsters: A suitable alternative to retrobulbar technique that provides large volumes and minimizes tissue damage.Lab. Anim.200943325526010.1258/la.2008.00707319237457
    [Google Scholar]
  45. ZhangY. HuoM. ZhouJ. XieS. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel.Comput. Methods Programs Biomed.201099330631410.1016/j.cmpb.2010.01.00720176408
    [Google Scholar]
  46. European Medicines AgencyICH. Topic Q2 (R1) Validation of analytical procedures: Text and methodology (CPMP/ ICH/ 381/ 95).1995Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-2-r1-validation-analytical-procedures-text-methodology-step-5_en.pdf accessed on 2023 Apr 14]
    [Google Scholar]
  47. GeorgievK. ZhelevI. GeorgievaS. Total phenolic compounds and tannins content of Bancha green tea (Camellia Sinensis) depending on extraction conditions.Scripta Scientifica Pharmaceutica201411485110.14748/ssp.v1i1.605
    [Google Scholar]
  48. SaklarS. ErtasE. OzdemirI.S. KaradenizB. Effects of different brewing conditions on catechin content and sensory acceptance in Turkish green tea infusions.J. Food Sci. Technol.201552106639664610.1007/s13197‑015‑1746‑y26396411
    [Google Scholar]
  49. GeorgievK. IlievI. JelevI. Evaluation of antitumor effect of methylxanthine fraction isolated from Pu-erh tea.World J. Pharm. Res.20154722362242
    [Google Scholar]
  50. JinY. JinC.H. Ho RowK. Separation of catechin compounds from different teas.Biotechnol. J.20061220921310.1002/biot.20050001916892250
    [Google Scholar]
  51. CsuporD. BorosK. JedlinszkiN. Theanine and Caffeine content of infusions prepared from commercial tea samples.Pharmacogn. Mag.20161245757910.4103/0973‑1296.17606127019564
    [Google Scholar]
  52. MohammedS.F. TadesseA. HymeteA. BekhitA.A. Quantification of total polyphenols, catechin, caffeine, L-theanine, determination of antioxidant activity and effect on antileishmanial drugs of ethiopian tea leaves extracts.Pharmacognosy Res.201575Suppl. 1710.4103/0974‑8490.15799126109792
    [Google Scholar]
  53. TfouniS.A.V. CamaraM.M. KamikataK. GomesF.M.L. FurlaniR.P.Z. Caffeine in teas: Levels, transference to infusion and estimated intake.Food Sci Technol201838466166610.1590/1678‑457x.12217
    [Google Scholar]
  54. KodamaD.H. GonçalvesA.E.S.S. LajoloF.M. GenoveseM.I. Flavonoids, total phenolics and antioxidant capacity: Comparison between commercial green tea preparations.Food Sci Technol20103041077108210.1590/S0101‑20612010000400037
    [Google Scholar]
  55. TeschkeR. XuanT.D. How can green tea polyphenols affect drug metabolism and should we be concerned?Expert Opin. Drug Metab. Toxicol.2019151298999110.1080/17425255.2019.169722831774338
    [Google Scholar]
  56. HodgesR.E. MinichD.M. Modulation of metabolic detoxification pathways using foods and food-derived components: A scientific review with clinical application.J. Nutr. Metab.2015201512310.1155/2015/76068926167297
    [Google Scholar]
  57. GeorgievK.D. Radeva-IlievaM. StoevaS. ZhelevI. Isolation, analysis and in vitro assessment of CYP3A4 inhibition by methylxanthines extracted from Pu-erh and Bancha tea leaves.Sci. Rep.2019911394110.1038/s41598‑019‑50468‑731558747
    [Google Scholar]
  58. JonesM.J. GroholJ. Internet-based prescription of sildenafil: A 2104-patient series.J. Med. Internet Res.200131E210.2196/jmir.3.1.e211720944
    [Google Scholar]
  59. Food and drug administration. Guidance for industry: Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteersAvailable from: https://www.fda.gov/media/72309/download2022 Jul 23].
  60. European Medicines AgencySummary of product characteristics.Available from: https://www.ema.europa.eu/en/documents/product-information/viagra-epar-product-information_en.pdf[accessed on 2022 Jul 20].
    [Google Scholar]
  61. AbdullaM. MallahE. Abu DayyihW. Influence of energy drinks on pharmacokinetic parameters of sildenafil in rats.Biomed. Pharmacol. J.20181131317132810.13005/bpj/1494
    [Google Scholar]
  62. SongY. LiC. LiuG. Drug-metabolizing cytochrome P450 enzymes have multifarious influences on treatment outcomes.Clin. Pharmacokinet.202160558560110.1007/s40262‑021‑01001‑533723723
    [Google Scholar]
  63. TeoY.L. HoH.K. ChanA. Metabolism‐related pharmacokinetic drug−drug interactions with tyrosine kinase inhibitors: Current understanding, challenges and recommendations.Br. J. Clin. Pharmacol.201579224125310.1111/bcp.1249625125025
    [Google Scholar]
  64. CaiZ.Y. LiX.M. LiangJ.P. Bioavailability of tea catechins and its improvement.Molecules2018239234610.3390/molecules2309234630217074
    [Google Scholar]
  65. ChuK.O. PangC.C. Pharmacokinetics and disposition of Green tea catechins. In: Malangu N, Ed.Pharmacokinetics and adverse effects of drugs – mechanisms and risks factors. MalanguN. LondonIntechOpen201810.5772/intechopen.74190
    [Google Scholar]
  66. MisakaS. KawabeK. OnoueS. Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats.Drug Metab. Pharmacokinet.201328651451810.2133/dmpk.DMPK‑13‑NT‑00623698259
    [Google Scholar]
  67. MeyboodiM. MohammadpourA.H. EmamiS.A. KarbasforooshanH. Drug interactions of green tea.J Pharm Care20218419620310.18502/jpc.v8i4.5243
    [Google Scholar]
  68. MustherH. Olivares-MoralesA. HatleyO.J.D. LiuB. Rostami HodjeganA. Animal versus human oral drug bioavailability: Do they correlate?Eur. J. Pharm. Sci.20145710028029110.1016/j.ejps.2013.08.01823988844
    [Google Scholar]
  69. WangL. PrasadB. SalphatiL. Interspecies variability in expression of hepatobiliary transporters across human, dog, monkey, and rat as determined by quantitative proteomics.Drug Metab. Dispos.201543336737410.1124/dmd.114.06158025534768
    [Google Scholar]
  70. ToutainP-L. FerranA. Bousquet-MélouA. Species differences in pharmacokinetics and pharmacodynamics. In: Cunningham F, Elliott J, Lees P, EdsComparative and Veterinary Pharmacology. CunninghamF. ElliottJ. LeesP. Berlin, HeidelbergSpringer Berlin Heidelberg2010194810.1007/978‑3‑642‑10324‑7_2
    [Google Scholar]
  71. BaeS.H. BaeS.K. LeeM.G. Effect of hepatic CYP inhibitors on the metabolism of sildenafil and formation of its metabolite, N-desmethylsildenafil, in rats in vitro and in vivo.J. Pharm. Pharmacol.200961121637164210.1211/jpp/61.12.000819958586
    [Google Scholar]
  72. ShinH. BaeS. LeeM. Pharmacokinetics of sildenafil after intravenous and oral administration in rats: Hepatic and intestinal first-pass effects.Int. J. Pharm.20063201-2647010.1016/j.ijpharm.2006.04.00516730145
    [Google Scholar]
/content/journals/ctm/10.2174/0122150838305894240724112703
Loading
/content/journals/ctm/10.2174/0122150838305894240724112703
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test