Skip to content
2000
Volume 17, Issue 3
  • ISSN: 2949-6810
  • E-ISSN: 2949-6829

Abstract

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease which leads to pain and disability that may trigger anxiety and sleep disturbances. Naproxen and St. John’s Wort concomitant administration in RA and anxiety raises the question of safety due to a potential drug interaction.

Materials and Methods

Albino Wistar rats were treated with naproxen and St. John’s Wort for 30 days. The study involved the evaluation of safety of naproxen when combined with St. John’s Wort by estimation of biochemical markers such as SGOT, SGPT, TG’s, Creatinine, BUN, the extent of gastromucosal damage and estimation of AUC, t1/2 and Clearance using blood serum analysis with HPLC after 30 days of treatment. Histopathological studies were also conducted to determine the tissue architecture.

Results

Elevated levels of hepatic markers SGOT, SGPT, TG, and gastro-mucosal damage with enhanced ulcer index were found in naproxen-St. John’s Wort treated rats as compared to only naproxen treated rats. HPLC analysis displayed increased AUC and t1/2 of naproxen with decreased clearance in naproxen-St. John’s Wort treated rats. Histopathological findings revealed tissue rupture and mucosal damage supporting the naproxen toxicity.

Conclusion

Consulting a healthcare professional before combining St. John's Wort with naproxen is essential to assess potential risks, manage drug interactions, and ensure safety. Personalized advice helps optimize treatment outcomes for both rheumatoid arthritis and mental health.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/dmbl/10.2174/0118723128356859250220063938
2025-02-27
2025-10-29

  • From This Site

    /content/journals/dmbl/10.2174/0118723128356859250220063938
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AndersonL.L. BernsE.J. BuggaP. GeorgeA.L.Jr MrksichM. Measuring drug metabolism kinetics and drug–drug interactions using self-assembled monolayers for matrix-assisted laser desorption-ionization mass spectrometry.Anal. Chem.201688178604860910.1021/acs.analchem.6b01750 27467208
     [Google Scholar]
  2. BushraR. AslamN. KhanA. Food-drug interactions.Oman Med. J.2011262778310.5001/omj.2011.21 22043389
     [Google Scholar]
  3. PonteloB.M. GrecoD.B. GuimarãesN.S. RotsenN. BragaV.A.R. PimentelP.H.N. BarbosaH. BarrosoT.M. TupinambásU. Profile of drug-drug interactions and impact on the effectiveness of antiretroviral therapy among patients living with HIV followed at an Infectious Diseases Referral Center in Belo Horizonte, Brazil.Braz. J. Infect. Dis.202024210410910.1016/j.bjid.2020.03.006 32360120
     [Google Scholar]
  4. KoziolekM. AlcaroS. AugustijnsP. BasitA.W. GrimmM. HensB. HoadC.L. JedamzikP. MadlaC.M. MaliepaardM. MarcianiL. MarucaA. ParrottN. PávekP. PorterC.J.H. ReppasC. van Riet-NalesD. RubbensJ. StatelovaM. TrevaskisN.L. ValentováK. VertzoniM. ČepoD.V. CorsettiM. The mechanisms of pharmacokinetic food-drug interactions – A perspective from the UNGAP group.Eur. J. Pharm. Sci.2019134315910.1016/j.ejps.2019.04.003 30974173
     [Google Scholar]
  5. RodriguesM.C.S. OliveiraC. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: An integrative review.Rev. Lat. Am. Enfermagem201624e280010.1590/1518‑8345.1316.2800
     [Google Scholar]
  6. GuQ. Prescription drug use continues to increase: US prescription drug data for 2007-2008.US Department of Health and Human Services2010
     [Google Scholar]
  7. PalleriaC. Di PaoloA. GiofrèC. CagliotiC. LeuzziG. SiniscalchiA. De SarroG. GallelliL. Pharmacokinetic drug-drug interaction and their implication in clinical management.J. Res. Med. Sci.2013187601610 24516494
     [Google Scholar]
  8. AbdoM.S. HammadM.A. HarunS.N. EusoffT.M. GhadziS.M.S. Evaluation of knowledge, attitude and practice of healthcare providers towards lifethreatening drug-drug interactions in Penang General Hospital, Malaysia.Clin. Epidemiol. Glob. Health202081253125810.1016/j.cegh.2020.04.023
     [Google Scholar]
  9. WójcikowskiJ. DanekP.J. Basińska-ZiobrońA. PukłoR. DanielW.A. In vitro inhibition of human cytochrome P450 enzymes by the novel atypical antipsychotic drug asenapine: A prediction of possible drug-drug interactions.Pharmacol. Rep.2020723612621
     [Google Scholar]
  10. ZhangD. ZhuM. HumphreysW.G. Drug Metabolism in Drug Design and Development: BASIC Concepts and Practice.John Wiley & Sons200710.1002/9780470191699
     [Google Scholar]
  11. LeeD.M. WeinblattM.E. Rheumatoid arthritis.Lancet2001358928590391110.1016/S0140‑6736(01)06075‑5 11567728
     [Google Scholar]
  12. Díaz-GonzálezF. Hernández-HernándezM.V. Rheumatoid arthritis.Med. Clin.20231611253354210.1016/j.medcle.2023.07.008
     [Google Scholar]
  13. RaduA.F. BungauS.G. Management of Rheumatoid arthritis: An overview.Cells20211011285710.3390/cells10112857 34831081
     [Google Scholar]
  14. BrownP. PrattA.G. HyrichK.L. Therapeutic advances in rheumatoid arthritis.BMJ2024384e07085610.1136/bmj‑2022‑070856 38233032
     [Google Scholar]
  15. ScottD.L. WolfeF. HuizingaT.W. Artritisreumatoide.Lancet201037697461094109810.1016/S0140‑6736(10)60826‑4 20870100
     [Google Scholar]
  16. KaratasG. BalA. YuceegeM. YalcinE. FiratH. DulgerogluD. KarataşF. SahinS. CakciA. ArdicS. The evaluation of sleep quality and response to anti-tumor necrosis factor α therapy in Rheumatoid arthritis patients.Clin. Rheumatol.2017361455010.1007/s10067‑016‑3387‑6 27567629
     [Google Scholar]
  17. SostresC. GargalloC.J. ArroyoM.T. LanasA. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract.Best Pract. Res. Clin. Gastroenterol.201024212113210.1016/j.bpg.2009.11.005 20227026
     [Google Scholar]
  18. SmithJ.B. HaynesM.K. Rheumatoid arthritis--A molecular understanding.Ann. Intern. Med.20021361290892210.7326/0003‑4819‑136‑12‑200206180‑00012 12069565
     [Google Scholar]
  19. KöhlerO. BenrosM.E. NordentoftM. FarkouhM.E. IyengarR.L. MorsO. KroghJ. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: A systematic review and meta-analysis of randomized clinical trials.JAMA Psychiatry201471121381139110.1001/jamapsychiatry.2014.1611 25322082
     [Google Scholar]
  20. McInnesI.B. SchettG. The pathogenesis of Rheumatoid arthritis.N. Engl. J. Med.2011365232205221910.1056/NEJMra1004965 22150039
     [Google Scholar]
  21. RainsfordK.D. Pharmacology and Toxicology of COX-2 Inhibitors. InCOX-2 Inhibitors.BaselBirkhäuser Basel200467131
     [Google Scholar]
  22. Patiño-CamachoS.I. MorenoM.G.L. Flores-MurrietaF.J. Déciga-CamposM. The pharmacokinetic profile of the combination of naproxen and tizanidine in rat.Drug Dev. Res.2013741313710.1002/ddr.21053
     [Google Scholar]
  23. SehonovaP. PlhalovaL. BlahovaJ. DoubkovaV. ProkesM. TichyF. FiorinoE. FaggioC. SvobodovaZ. Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages.Chemosphere201718841442310.1016/j.chemosphere.2017.08.151 28898774
     [Google Scholar]
  24. MalhiG.S. MannJ.J. Depression.Lancet2018392101612299231210.1016/S0140‑6736(18)31948‑2 30396512
     [Google Scholar]
  25. NairA. JacobS. A simple practice guide for dose conversion between animals and human.J. Basic Clin. Pharm.201672273110.4103/0976‑0105.177703 27057123
     [Google Scholar]
  26. DuvalF. LebowitzB.D. MacherJ.P. Treatments in depression.Dialogues Clin. Neurosci.20068219120610.31887/DCNS.2006.8.2/fduval 16889105
     [Google Scholar]
  27. CarazoA. DusekJ. HolasO. SkodaJ. HyrsovaL. SmutnyT. SoukupT. DosedelM. PávekP. Teriflunomide is an indirect human constitutive androstane receptor (CAR) activator interacting with epidermal growth factor (EGF) signaling.Front. Pharmacol.2018999310.3389/fphar.2018.00993 30364229
     [Google Scholar]
  28. FeketeF. MenusÁ. TóthK. KissÁ.F. MinusA. SirokD. BeličA. PótiÁ. CsuklyG. MonostoryK. CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients.Sci. Rep.20231311850710.1038/s41598‑023‑45752‑6 37898643
     [Google Scholar]
  29. DenisovI.G. MakrisT.M. SligarS.G. SchlichtingI. Structure and chemistry of cytochrome P450.Chem. Rev.200510562253227810.1021/cr0307143 15941214
     [Google Scholar]
  30. PelkonenO. NebertD.W. Metabolism of polycyclic aromatic hydrocarbons: Etiologic role in carcinogenesis.Pharmacol. Rev.1982342189222 6287505
     [Google Scholar]
  31. ZhouS.F. YangL.P. ZhouZ.W. LiuY.H. ChanE. Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2.AAPS J.200911348149410.1208/s12248‑009‑9127‑y 19590965
     [Google Scholar]
  32. van DelftM.A.M. VerheulM.K. BurgersL.E. DerksenV.F.A.M. van der Helm-van MilA.H.M. van der WoudeD. HuizingaT.W.J. ToesR.E.M. TrouwL.A. The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients.Arthritis Res. Ther.201719119010.1186/s13075‑017‑1392‑z 28810902
     [Google Scholar]
  33. GuengerichF.P. Cytochrome p450 and chemical toxicology.Chem. Res. Toxicol.2008211708310.1021/tx700079z 18052394
     [Google Scholar]
  34. SeistG. Need for pharmacogenomic information also for generic medications: Recommendation of the European Society of Pharmacogenomics and Theranostics (ESPT).dmdi201227211910.1515/dmdi‑2012‑0010 22706235
     [Google Scholar]
  35. ManikandanP. NaginiS. Cytochrome P450 structure, function and clinical significance: A review.Curr. Drug Targets20181913854 28124606
     [Google Scholar]
  36. BorrelliF. IzzoA.A. Herb-drug interactions with St John’s wort (Hypericum perforatum): An update on clinical observations.AAPS J.200911471072710.1208/s12248‑009‑9146‑8 19859815
     [Google Scholar]
  37. NovelliM. MasielloP. BeffyP. MenegazziM. Protective role of St. John’s wort and its components hyperforin and hypericin against diabetes through inhibition of inflammatory signaling: Evidence from in vitro and in vivo studies.Int. J. Mol. Sci.20202121810810.3390/ijms21218108 33143088
     [Google Scholar]
  38. TedeschiE. MenegazziM. MargottoD. SuzukiH. ForstermannU. KleinertH. Anti-inflammatory actions of St John’s wort: Inhibition of human iNOS expression by down regulating STAT-1 α activation.J. Pharmacol. Exp. Ther.200330725426110.1124/jpet.103.054460
     [Google Scholar]
  39. KamalianA. AslM.S. DolatshahiM. AfshariK. ShamshiriS. RoudsariN.M. MomtazS. RahimiR. AbdollahiM. AbdolghaffariA.H. Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways.World J. Gastroenterol.202026243365340010.3748/wjg.v26.i24.3365 32655263
     [Google Scholar]
  40. VerreJ. BoissonM. PaumierA. TriboloS. BoujedainiN. Anti-inflammatory effects of Arnica montana (mother tincture and homeopathic dilutions) in various cell models.J. Ethnopharmacol.2024318Pt B11706410.1016/j.jep.2023.117064 37598770
     [Google Scholar]
/content/journals/dmbl/10.2174/0118723128356859250220063938
Loading
Evaluating the Influence of St. John’s Wort on Naproxen Pharmacokinetics and Pharmacodynamics: A Drug Interaction Assessment
Drug Metab. Bioanal. Lett. 17, 137 (2024); https://doi.org/10.2174/0118723128356859250220063938
/content/journals/dmbl/10.2174/0118723128356859250220063938
/content/journals/dmbl/10.2174/0118723128356859250220063938
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): biochemical markers; drug interactions; gastromucosal; Naproxen; NSAID; rheumatoid arthritis; St. John’s Wort

Most Cited Most Cited RSS feed

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