Author(s):
Dipak Dadasaheb Nalawade, Jyoti Dattatray Anap, Vaishnavi Dnyandeo Charmal, Asha Changdev Halnor, Pratiksha Dagu Varpe
Email(s):
nalawadedipak6@gmail.com , anapjyoti123@gmail.com
DOI:
10.52711/2231-5691.2025.00065 
Address:
Dipak Dadasaheb Nalawade1*, Jyoti Dattatray Anap2, Vaishnavi Dnyandeo Charmal3, Asha Changdev Halnor4, Pratiksha Dagu Varpe5
1Assistant Professor, Department of Pharmaceutical Chemistry, Dr. Kolpe Institute of Pharmacy, Kolpewadi.
2Final Year B. Pharmacy Student, Dr. Kolpe Institute of Pharmacy, Kolpewadi.
3Final Year B. Pharmacy Student, Dr. Kolpe Institute of Pharmacy, Kolpewadi.
4Final Year B. Pharmacy Student, Dr. Kolpe Institute of Pharmacy, Kolpewadi.
5Second Year B. Pharmacy Student, Dr. Kolpe Institute of Pharmacy, Kolpewadi.
*Corresponding Author
Published In:
Volume - 15,
Issue - 4,
Year - 2025
ABSTRACT:
Methotrexate (MTX), a folate antagonist, has been widely used in cancer chemotherapy and autoimmune diseases since its development in the mid-20th century. It was first used in 1948 to treat leukemia, and in 1988 the FDA approved it for use in treating rheumatoid arthritis (RA). By suppressing dihydrofolate reductase, preventing DNA and RNA synthesis, and adjusting immunological responses, MTX works. MTX has side effects such as hepatotoxicity, hematological suppression, and pulmonary problems despite its effectiveness. MTX has a limited bioavailability at large oral doses and is categorized as a BCS Class IV medication because of its poor solubility and low permeability. It is metabolized by the liver and eliminated by the kidneys. The medicine is contraindicated in pregnant individuals and those with liver, renal, or lung disorders. Drug interactions are common, particularly when using PPIs and NSAIDs. Leucovorin rescue, urine alkalinization, and hemodialysis are used to treat overdoses of MTX, which comes in a variety of oral and injectable forms. Tetra aminopyrimidine is the beginning point for a series of chemical processes that make up its production. Despite the advent of more recent treatments, MTX continues to be a mainstay medication because of its several uses in rheumatology, dermatology, and oncology.
Cite this article:
Dipak Dadasaheb Nalawade, Jyoti Dattatray Anap, Vaishnavi Dnyandeo Charmal, Asha Changdev Halnor, Pratiksha Dagu Varpe. Methotrexate: A Pharmacological Powerhouse in Modern Therapeutics. Asian Journal of Pharmaceutical Research.2025; 15(4):418-4. doi: 10.52711/2231-5691.2025.00065
Cite(Electronic):
Dipak Dadasaheb Nalawade, Jyoti Dattatray Anap, Vaishnavi Dnyandeo Charmal, Asha Changdev Halnor, Pratiksha Dagu Varpe. Methotrexate: A Pharmacological Powerhouse in Modern Therapeutics. Asian Journal of Pharmaceutical Research.2025; 15(4):418-4. doi: 10.52711/2231-5691.2025.00065 Available on: https://asianjpr.com/AbstractView.aspx?PID=2025-15-4-11
REFERENCE:
1. Hamed K M, et al. Overview of Methotrexate Toxicity: A Comprehensive Literature Review. Cureus. 14(9): e29518. DOI 10.7759/cureus.29518
2. Methotrexate - Wikipedia https://en.m.wikipedia.org/wiki/Methotrexate
3. Anand, N. Malaviya, Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story, International Journal of Rheumatic Diseases. 2016; 19: 844–851; https://onlinelibrary.wiley.com/doi/abs/10.1111/1756-185X.12862
4. Methotrexate sodium Injection USP monograph – United States Pharmacopeia
5. https://pubchem.ncbi.nlm.nih.gov/compound/Methotrexate#section=InChI
6. Silverstein, Webster, Kiemle - Spectrometric Identification of Organic Compounds
7. Indian Pharmacopoeia 2010 - volume 2
8. Giri, B.R.; et. al Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium. Pharmaceutics. 2021; 13(1): 111; https://doi.org/10.3390/pharmaceutics13010111
9. Bedoui Y, et.al Methotrexate an Old Drug with New Tricks. Int J Mol Sci. 2019 Oct 10; 20(20): 5023. doi: 10.3390/ijms20205023
10. Methotrexate: Uses, Interactions, Mechanism of Action | DrugBank Online https://go.drugbank.com/drugs/DB00563
11. https://www.ncbi.nlm.nih.gov/books/NBK556114/
12. https://www.sciencedirect.com/topics/chemistry/methotrexate
13. Chabner, B. A., and Longo, D. L. (2011). Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott Williams and Wilkins.
14. Singh, J. A., et al. American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis and Rheumatology. 2016; 68(1): 1–26.
15. Menter, A., et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2009; 61(3): 451–485.
16. Barnhart, K. Ectopic Pregnancy. New England Journal of Medicine. 2009; 361(4): 379–387.
17. Lichtenstein, G. R., et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018; 113(4): 481–517.
18. McCune, J. S., and Clark, M. A. The Pharmacology of Methotrexate in Rheumatology and Cancer. Clinical Pharmacology and Therapeutics. 2011; 90(1): 1-5.
19. Lichtenstein, G. R., and Yajnik, V. Methotrexate-induced Hematologic Toxicity in Inflammatory Bowel Disease. Journal of Clinical Gastroenterology. 2003; 37(4): 243-249.
20. Miele, L., and Cicala, M. Hepatotoxicity of Methotrexate in Rheumatologic Therapy. Digestive and Liver Disease. 2006; 38(2): 116-123.
21. Kähler, C. M., and Eberhard, L. Pulmonary Toxicity Induced by Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review. Journal of Rheumatology. 2012; 39(5): 912-917.
22. Weiner, M., and Press, O. W. Renal Toxicity of Methotrexate: Mechanisms and Management. Seminars in Oncology. 2009; 36(4): 289-297
23. Moxley, G. M., and Smith, P. Methotrexate in the Treatment of Rheumatoid Arthritis and Pregnancy Considerations. American Journal of Obstetrics and Gynecology. 2007; 197(5): 457.e1-457.e7.
24. Fisher, B. Folinic acid rescue for methotrexate overdose. Seminars in Oncology. 1994; 21(6): 689-694.
25. Chan, S., et al. Management of methotrexate overdose. Journal of Clinical Pharmacology. 2017; 57(9): 1050-1057.
26. Hayes, T. G., et al. Management of high-dose methotrexate toxicity. Journal of Oncology Pharmacy Practice. 2019; 25(2): 408-418.
27. McAlister, D. R., et al. Methotrexate overdose: A review of current management practices. Pharmacotherapy. 2018; 38(12): 1262-1274.
28. National Formulary of India 4th Edition 2011, 648-695
29. https://www.netmeds.com/prescriptions/methotrexate -1ml
30. https://www.apollopharmacy.in/medicine/methotrexate-2-5mg-tablet?srsltid=AfmBOoolW11FeNqm6stqOtZrPvcpBktzlvEGqrc8hYjUhXLyi9bxO-zq
31. Benians, P. R. (2016). Methotrexate compositions for oral administration. U.S. Patent No. 9,259,427. Washington, DC: U.S. Patent and Trademark Office. https://patents.google.com/patent/US9259427B2
32. Benians, P. R. (2019). Methotrexate compositions for oral administration. U.S. Patent No. 10,231,927. Washington, DC: USPTO. https://patents.google.com/patent/US10231927B2
33. Benians, P. R. (2020). Methotrexate compositions for oral administration. U.S. Patent No. 10,610,485. Washington, DC: USPTO. https://patents.google.com/patent/US10610485B2
34. Henshall, C. (2021). Methotrexate pharmaceutical compositions. U.S. Patent No. 11,129,833. Washington, DC: USPTO. https://patents.google.com/patent/US11129833B2
35. Ruangwattanasuk, O. (2021). Methotrexate derivatives and methods of treatment. U.S. Patent No. 11,129,899. Washington, DC: USPTO. https://patents.google.com/patent/US11129899B2
36. Horwitz, R. S. (2007). Parenteral methotrexate compositions. U.S. Patent No. 7,229,623. Washington, DC: USPTO. https://patents.google.com/patent/US7229623B2