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Abstract

Ulcers, particularly peptic ulcers, have long been a significant medical concern, with potential complications ranging from discomfort to life-threatening hemorrhage. Over the years, numerous antiulcer agents have been developed and introduced into clinical practice, aiming to alleviate symptoms, promote healing, and prevent recurrence. This review delves into the recent advancements in the clinical evaluation of these agents, highlighting the methodologies employed, the efficacy observed, and the safety profiles established. Recent studies have emphasized the importance of a multifaceted approach to the clinical evaluation of antiulcer agents. Beyond merely assessing symptomatic relief, researchers now focus on mechanisms of action, pharmacokinetics, and pharmacodynamics to provide a comprehensive understanding of drug efficacy. Advanced imaging techniques, such as endoscopy and capsule endoscopy, have enabled real-time visualization of ulcer healing, facilitating a more precise assessment of therapeutic outcomes. Safety remains paramount in the evaluation of antiulcer agents, with recent research focusing on the identification and mitigation of adverse effects, drug interactions, and long-term complications. The integration of patient-reported outcomes and quality-of-life assessments has further enriched our understanding of the overall impact of antiulcer therapy on patient well-being.

Keywords

Target Therapy, Signs and Symptoms , Complication, List of Withdrawn Drugs, Commonly used antiulcer drugs, Clinical trials phases, Preclinical

Reference

  1. Yuan Y, Padol IT, Hunt RH: Peptic ulcer disease today. Nat Clin Pract Gastroenterol Hepatol 2006;3:80-89.
  2. F. K. L. Chan and D. Y. Graham, “Review article: prevention of non-steroidal anti-inflammatory drug gastrointestinal complications—review and recommendations based on risk assessment,” Alimentary Pharmacology and Therapeutics, vol. 19, no. 10, pp. 1051–1061, 2004.
  3. B. Debjit, C. Chiranjib, K. K. Tripathi, Pankaj, and K. P. Sampath Kumar, “Recent trends of treatment and medication peptic ulcerative disorder,” International Journal of PharmTech Research, vol. 2, no. 1, pp. 970–980, 2010.
  4. B. J. Marshall and J. R. Warren, “Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration,” The Lancet, vol. 1, no. 8390, pp. 1311–1315, 1984.
  5. Mishra, A. P., Bajpai, A., & Chandra, S. (2019). A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antiulcer Drugs. Current clinical pharmacology, 14(3), 175–196.
  6. Adinortey MB, Ansah C, Galyuon I, Nyarko A.(2013) In vivo models used for evaluation of potential antigastroduodenal ulcer agents ulcers. 1–12.
  7. Harsh Mohan. Text book of pathology .sixth edition, jaypee publishers. 2009, 549-555
  8. S. M. K. Rates, “Plants as source of drugs,” Toxicon, vol. 39, no. 5, pp. 603–613, 2001.      
  9. P.; Chan, F.K.; McColl, K. EL Peptic ulcer disease. Lancet 2009, 374, 1449–1461.
  10. W.D.; Wong, B.C.Y. Practice Parameters Committee of the American College of Gastroenterology American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection. Am. J. Gastroenterol. 2007, 102, 1808–1825.
  11. K.M.; Katelaris, P.; Sugano, K.; Ang, T.L.; Hunt, R.; Talley, N.J.; Lam, S.K.; Xiao, S.-D.; Tan, H.J.; Wu, C.-Y.; et al. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J. Gastroenterol. Hepatol. 2009, 24, 1587–1600
  12. Fallone, C.A.; Chiba, N.; van Zanten, S.V.; Fischbach, L.; Gisbert, J.P.; Hunt, R.H.; Jones, N.L.; Render, C.; Leontiadis, G.I.; Moayyedi, P.; et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology 2016, 151, 51–69.
  13. Amaral, G.P.; de Carvalho, N.R.; Barcelos, R.P.; Dobrachinski, F.; de Lima Portella, R.; da Silva, M.H.; Lugokenski, T.H.; Dias, G.R.M.; da Luz, S.C.A.; Boligon, A.A.; et al. Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats. Food Chem. Toxicol. 2013, 55, 48–55.
  14. Broutet, N.; Tchamgoué, S.; Pereira, E.; Lamouliatte, H.; Salamon, R.; Mégraud, F. Risk factors for failure of Helicobacter pylori therapy--results of an individual data analysis of 2751 patients. Aliment. Pharmacol. Ther. 2003, 17, 99–109.
  15. Nezami B.G., Jani M., Alouani D., Rhoads D.D., Sadri N. Helicobacter pylori Mutations Detected by Next-Generation Sequencing in Formalin-Fixed, Paraffin-Embedded Gastric Biopsy Specimens Are Associated with Treatment Failure. J. Clin. Microbiol. 2019;57:e01834-18. doi: 10.1128/JCM.01834-18.
  16. Ferreira R.M., Pereira-Marques J., Pinto-Ribeiro I., Costa J.L., Carneiro F., Machado J.C., Figueiredo C. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut. 2018;67:226–236. doi: 10.1136/gutjnl-2017-314205.
  17. Malfertheiner P., Megraud F., O’Morain C.A., Gisbert J.P., Kuipers E.J., Axon A.T., Bazzoli F., Gasbarrini A., Atherton J., Graham D.Y., et al. European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66:6–30. doi: 10.1136/gutjnl-2016-312288.
  18. Zaki M., Coudron P.E., McCuen R.W., Harrington L., Chu S., Schubert M.L. H. Pylori acutely inhibits gastric secretion by activating CGRP sensory neurons coupled to stimulation of somatostatin and inhibition of histamine secretion. Am. J. Physiol. Gastrointest.LiverPhysiol. 2013;304:G715G722.doi: 10.1152/ajpgi.00187.2012.
  19. K. D. Rainsford, “The effects of 5-lipoxygenase inhibitors and leukotriene antagonists on the development of gastric lesions induced by nonsteroidal antiinflammatory drugs in mice,” Agents and Actions, vol. 21, no. 3-4, pp. 316–319, 1987.
  20. Scally, B.; Emberson, J.R.; Spata, E.; Reith, C.; Davies, K.; Halls, H.; Holland, L.; Wilson, K.; Bhala, N.; Hawkey, C.; et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: A meta-analysis of randomised trials. lancet. Gastroenterol. Hepatol. 2018, 3, 231–241. 
  21. Bhala N., Emberson J., Merhi A., Abramson S., Arber N., Baron J.A., Bombardier C., Cannon C., Farkouh M.E., FitzGerald G.A., et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: Meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769–779.
  22. DaCosta DiBonaventura M., Yuan Y., Wagner J.S., L’Italien G.J., Lescrauwaet B., Langley P. The burden of viral hepatitis C in Europe: A propensity analysis of patient outcomes. Eur. J. Gastroenterol. Hepatol. 2012;24:869–877. doi: 10.1097/MEG.0b013e3283551dee.
  23. K. D. Rainsford, “The effects of 5-lipoxygenase inhibitors and leukotriene antagonists on the development of gastric lesions induced by nonsteroidal antiinflammatory drugs in mice,” Agents and Actions, vol. 21, no. 3-4, pp. 316–319, 1987.
  24. Pfizer: XELJANZ gets marketing authorization in EU for ulcerative colitis. Available from: http://www.rttnews.com/2921111/pfizer-xeljanz-gets-marketing authorization-in-eu-for-ulcerative-colitis.asp
  25. Karner M, Kocjan A, Stein J, Schreiber S, von Boyen G, Uebel P, Schmidt C, Kupcinskas L, Dina I, Zuelch F, et al. First multicenter study of modified release phosphatidylcholine “LT-02” in ulcerative colitis: a randomized, placebo-controlled trial in mesalazine-refractory courses. Am J Gastroenterol. 2014;109:1041–1051.
  26. al. JAK inhibitors: novel developments in management of ulcerative colitis Best Pract Res Clin Gastroenterol (2018)
  27. H. Shay, S. A. Komarov, S. S. Fels, D. Meranze, M. Gruenstein, and H. Siplet, “A simple method for the uniform production of gastric ulceration in the rat,” Gastroenterology, vol. 5, pp. 43–61, 1945.
  28. E.M. Medicinal plants with antibacterial properties against helicobacter pylori: A brief review. Curr. Trends Nutraceuticals. 2016;1:3.
  29. Kulkarni SK: Handbook of Experimental Pharmacology. New Delhi, Vallabh Prakashan, 1999.
  30. Vogel HG: Drug Discovery and Evaluation, Pharmacological Assay. New York, Springer, 2002
  31. S (2013). SRB's Manual of Surgery. JP Medical. p. 364. ISBN 9789350259443.
  32. Acute vs. chronic conditions: MedlinePlus Medical Encyclopedia Image". medlineplus.gov. Retrieved 2019-08-30
  33. ZP; Seoane-Vazquez, E; Rodriguez-Monguio, R; Stevenson, KB; Szeinbach, SL (July 2011). "Market withdrawal of new molecular entities approved in the United States from 1980 to 2009". Pharmacoepidemiology and Drug Safety. 20 (7): 772–7.
  34. Fung, M.; Thornton, A.; Mybeck, K.; Wu, J. H.-h.; Hornbuckle, K.; Muniz, E. (1 January 2001). "Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999". Therapeutic Innovation & Regulatory Science. 35 (1): 293–317.
  35. Press release. London, UK: European Medicines Agency. 25 October 2011. Archived from the original on 28 October 2011. Retrieved 26 October 2011.
  36. Schubert-Zsilavecz, Manfred (2011). "Arzneimittelrücknahmen Rückrufe im Rückblick". Pharmazeutische Zeitung (German). Archived from the original on 27 September 2013. Retrieved 25 September 2013.
  37. Qureshi, ZP; Seoane-Vazquez, E; Rodriguez-Monguio, R; Stevenson, KB; Szeinbach, SL (July 2011). "Market withdrawal of new molecular entities approved in the United States from 1980 to 2009". Pharmacoepidemiology and Drug Safety. 20 (7): 772–7.
  38. Fung, M.; Thornton, A.; Mybeck, K.; Wu, J. H.-h.; Hornbuckle, K.; Muniz, E. (1 January 2001). "Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999". Therapeutic Innovation & Regulatory Science. 35 (1): 293–317.
  39. US Food and Drug Administration. 4 January 2018. Retrieved 17 August 2020.
  40. "Exploratory IND Studies, Guidance for Industry, Investigators, and Reviewers" (PDF). Food and Drug Administration. January 2006. Retrieved 2010-06-15.
  41. Lancet (July 2009). "Phase 0 trials: a platform for drug development?". Lancet. 374 (9685): 176. doi:10.1016/S0140-6736(09)61309-X. PMID 19616703. S2CID 30939770.
  42. Burt, Tal; Young, Graeme; Lee, Wooin; Kusuhara, Hiroyuki; Langer, Oliver; Rowland, Malcolm; Sugiyama, Yuichi (2020). "Phase 0/microdosing approaches: time for mainstream application in drug development?". Nature Reviews Drug Discovery. 19 (11): 801–818. doi:10.1038/s41573-020-0080-x. ISSN 1474-1784. PMID 32901140.
  43. JA (March 2015). "Feeding and Bleeding: The Institutional Banalization of Risk to Healthy Volunteers in Phase I Pharmaceutical Clinical Trials". Science, Technology, & Human Values. 40 (2):199226. doi:10.1177/0162243914554838. PMC 4405793. PMID 25914430.
  44. Jump up to:a b c d e f g "Types and phases of clinical trials". American Cancer Society. 18 August 2020. Retrieved 15 September 2020.
  45. "NCI Dictionary". National Cancer Institute. 2011-02-02.
  46. den Eynde BJ, van Baren N, Baurain JF (2020). "Is There a Clinical Future for IDO1 Inhibitors After the Failure of Epacadostat in Melanoma?". Annual Review of Cancer Biology. 4: 241–256. doi:10.1146/annurev-cancerbio-030419-033635.
  47. Jump up to:a b "Step 3. Clinical research". US Food and Drug Administration. 14 October 2016. Retrieved 1 February 2017.
  48. AE (2008). "The myth of equipoise in phase 1 clinical trials". Medscape Journal of Medicine. 10 (11): 254. PMC 2605120. PMID 19099004.(registration required)
  49. Jump up to:a b c d e f g h i DeMets D, Friedman L, Furberg C (2010). Fundamentals of Clinica Trials (4th ed.).
  50. Revive, Global Antiobiotic Research and Development Partnership. 2023. Retrieved 24 October 2023.
  51. Guidance for Institutional Review Boards and Clinical Investigators". Food and Drug Administration. 1999-03-16. Retrieved 2007-03-27.
  52. The regulatory authority in the US is the Food and Drug Administration; in Canada, Health Canada; in the European Union, the European Medicines Agency; and in Japan, the Ministry of Health, Labour and Welfare
  53. VP, Peterson AM (2005). Pharmacotherapeutics for Advanced Practice: A Practical Approach. Lippincott Williams & Wilkins. ISBN 978-0-7817-5784-3.

Photo
Tejaswini S. Kamble
Corresponding author

Department Of Pharmacology, Ashokrao Mane Institute Of Pharmacy, Ambap-416112, India

Photo
Vishavjeet S. Pisal
Co-author

Department Of Pharmacology, Ashokrao Mane Institute Of Pharmacy, Ambap-416112, India

Photo
Pritam Salokhe
Co-author

Department Of Pharmacology, Ashokrao Mane Institute Of Pharmacy, Ambap-416112, India

Photo
sachin Navale
Co-author

Department Of Pharmacology, Ashokrao Mane Institute Of Pharmacy, Ambap-416112, India

Photo
Nilesh Chougule
Co-author

Department Of Pharmacology, Ashokrao Mane Institute Of Pharmacy, Ambap-416112, India

Tejaswini Kamble, Vishavjeet Pisal, Pritam Salokhe, sachin Navale, Nilesh Chougule Recent Advances In Clinical Evaluation Of Antiulcer Drug, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 1, 513-525. https://doi.org/10.5281/zenodo.10557061

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