Review: Drug Discovery and Development of Warfarin
DOI:
https://doi.org/10.22270/ajprd.v10i4.1158Keywords:
Warfarin, Drug Discovery, Anticoagulants.Abstract
Background: The history of the discovery of Warfarin started from the plains of North America in Canada in 1920. Livestock in that area died from bleeding. Warfarin was first used in 1948 as a rodenticide, and in 1954 the US Food and Drug Administration (FDA) approved it for medical use as an anticoagulant.
Purpose: This review article aims to discuss the history of the discovery of warfarin starting from the presence of blood clotting disorders to the point that researchers worked to find drugs that can inhibit blood clotting, namely the anticoagulant group.
Research Methods: The method used is the study of relevant literature which is accessed through online sites such as Google Scholar, Research Gate, Science Direct, Springer Link, and NCBI.
Conclusion: In its development, several trials such as in silico, preclinical, and clinical trials have shown significant results but are always associated with bleeding.
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References
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24. Mcculloch, P, and W D George. 1989. “Warfarin Inhibits Metastasis of Mtln 3 Rat Affecting Primary Tumour Growth.” Cultures: 179–83.
25. Smith, G. F., Neubauer, B. L., Sundboom, J. L., Best, K. L., Goode, R. L., Tanzer L. R., Merriman, R. L., Frank, J. D., and Herrmann, R. G. Correlation of The In Vivo Anticoagulant, Antithrombotic and Antimetastatic. Thrombosis Research. 1988; 50(1):163-174.
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28. Pharmacology, O P. 1978. “Of Ventilation by Warfarin1.”
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30. Foerch, Christian Arai, Ken Jin, Guang Park, Kyung Pil Pallast, Stefanie Van Leyen, Klaus Lo, Eng H. “Experimental Model of Warfarin-Associated Intracerebral Hemorrhage.” Stroke 2008; 39(12):3397–3404.
31. Krüger, Thilo Oelenberg, Stephan Kaesler, Nadine Schurgers, Leon J. Van De Sandt, Annette M. Boor, Peter Schlieper, Georg Brandenburg, Vincent M. Fekete, Bertalan C. Veulemans, Verena Ketteler, Markus Vermeer, Cees Jahnen-Dechent, Willi Floege, Jürgen Westenfeld, Ralf. 2013. “Warfarin Induces Cardiovascular Damage in Mice.” Arteriosclerosis, Thrombosis, and Vascular Biology 33(11): 2618–24.
32. Akdeniz, Universitas. 2014. “Diterjemahkan Dari Bahasa Turki Ke Bahasa Indonesia - Www.Onlinedoctranslator.Com.” : 101–25.
33. Colvin, H W, and W L E E Wang. 1974. “Toxic Effects of Warfarin in Rats Fed Different Diets Male Sprague-Dawley Rats , Weighing 250-300 g , Were Individually Caged in a Room Maintained at 22 ° C . One Group of 30 Rats Was Fed a Diet of Purina Laboratory Chow , l Hereafter Called ‘ Chow ’ ( Pr.” :1974; 337–48.
34. Alaydrus, H. 2015. “Mikroskopis Otak Dan Hati Pada Tikus Wistar Setelah Pemberian Warfarin Ld-50 Dan Ld-100.” 4(4): 933–47.
35. Howe, Andrew M., and Williams S. Webster.“Exposure of the Pregnant Rat to Warfarin and Vitamin K1: An Animal Model of Intraventricular Hemorrhage in the Fetus.” Teratology 1990; 42(4): 413–20.
36. Choonara, IA Malia, RG Haynes, BP Hay, CR Cholerton, S. Breckenridge, AM Preston, FE Park, BK. “The Relationship between Inhibition of Vitamin K1 2,3‐epoxide Reductase and Reduction of Clotting Factor Activity with Warfarin.” British Journal of Clinical Pharmacology 1988; 25(1): 1–7.
37. Krishnan, Subramanian, Namrata Chawla, Michael D. Ezekowitz, and Aldo J. Peixoto. “Warfarin Therapy and Systolic Hypertension in Men with Atrial Fibrillation.” American Journal of Hypertension 2005; 18(12):1592–99.
38. EKİZ, Mehmet, Latif DURAN, Hızır Ufuk AKDEMİR, and İskender AKSOY. “The Factors Associated With Bleeding in Patients Using Warfarin.” Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 2021; 23(3):482–91.
39. Finazzi, G. Brancaccio, V. Schinco, P. Wisloff, F. Musial, J. Baudo, F. Berrettini, M. Testa, S. D'Angelo, A. Tognoni, G. Barbui, T. Marchioli, Roberto. 2005. “A Randomized Clinical Trial of High-Intensity Warfarin vs. Conventional Antithrombotic Therapy for the Prevention of Recurrent Thrombosis in Patients with the Antiphospholipid Syndrome (WAPS).” Journal of Thrombosis and Haemostasis 3(5): 848–53.
40. Cheng, Alan Nazarian, Saman Brinker, Jeffrey A. Tompkins, Christine Spragg, David D. Leng, Charles T. Halperin, Henry Tandri, Harikrishna Sinha, Sunil K. Marine, Joseph E. Calkins, Hugh Tomaselli, Gordon F. Berger, Ronald D. Henrikson, Charles A.. 2011. “Continuation of Warfarin during Pacemaker or Implantable Cardioverter-Defibrillator Implantation: A Randomized Clinical Trial.” Heart Rhythm 2011; 8(4):536–40. http://dx.doi.org/10.1016/j.hrthm.2010.12.016.
41. Albert Schweitzer Hospital, Lambarene, Gabon, and Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.“Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation.” New England Journal of Medicine 2011; 365:687–96.
42. Mette, Hurlen, Abdelnoor, Mchael A Ål, P Mith, S An, J Rikssen, E. “The New England Journal of Medicine Warfarin, Aspirin, Or Both After Myocardial Infarction Background The Role of Antithrombotic Therapy In.” N Engl J Med 2002; 347(13):969–74. www.nejm.org.
43. Lotke, Paul A. Callaghan, John J. Dorr, Lawrence D. Engh, Gerard H. Hanssen, Arlen D. Healy, William L. Lachiewicz, Paul F. Lonner, Jess H. Nelson, Charles Ranawat, Chitranjan S. Ritter, Merrill A. Salvati, Eduarde A. Sculco, Thomas P. Thornhill, Thomas S. “Oral Direct Thrombin Inhibitor Ximelagatran Compared with Warfarin for the Prevention of Venous Thromboembolism after Total Knee Arthroplasty [9].” Journal of Bone and Joint Surgery - Series A 2006; 88(5):1163.
44. Al-Khatib, Sana M. Thomas, Laine Wallentin, Lars Lopes, Renato D. Gersh, Bernard Garcia, David Ezekowitz, Justin Alings, Marco Yang, Hongqui Alexander, John H. Flaker, Gregory Hanna, Michael Granger, Christopher B. “Outcomes of Apixaban vs. Warfarin by Type and Duration of Atrial Fibrillation: Results from the ARISTOTLE Trial.” European Heart Journal 2013; 34(31):2464–71.
45. Oates, A., P. R. Jackson, C. A. Austin, and K. S. Channer. “A New Regimen for Starting Warfarin Therapy in Out-Patients.” British Journal of Clinical Pharmacology 1998; 46(2):157–61.
46. Jeong, Jong-woo, Youngshin Song, and Tae-sung Koo. “Effects of Formulation Types on Pharmacodynamics of Warfarin in Patients with Cerebral Infarction and Dysphagia.” : 51–56.
47. Klang, Mark, Dennis Graham, and Veronica McLymont. “Warfarin Bioavailability with Feeding Tubes and Enteral Formula.” Journal of Parenteral and Enteral Nutrition 2010; 34(3): 300–304.
48. Sharley, Nicholas A., Annie M.C. Yu, and Desmond B. Williams.“Stability of Mixtures Formulated from Warfarin Tablets or Powder.” Journal of Pharmacy Practice and Research 2007; 37(2):95–97.
49. Schlatter, Joël, and Salvatore Cisternino. “Stability of Warfarin Sodium Flavoured Preservative-Free Oral Liquid Formulations.” European Journal of Hospital Pharmacy 2018; 25(e2): e98–101.
50. Abdallah, Siham, and Nourah A Al-abduwahed.“Availability and Stability of Crushed Warfarin Tablet in Different Solvents.” The Pharmaceutical and Chemical Journal 2016; 3(2):316–22.
2. Gupta, Rohan Srivastava, Devesh Sahu, Mehar Tiwari, Swati Ambasta, Rashmi K Kumar, Pravir. Molecular Diversity Artificial Intelligence to Deep Learning : Machine Intelligence Approach for Drug Discovery. Springer International Publishing. https://doi.org/10.1007/s11030-021-10217-3.
3. Hairunnisa, Hairunnisa. “Sulitnya Menemukan Obat Baru Di Indonesia.” Farmasetika.com (Online) 2019; 4(1):16.
4. Paul, G. 2015. “Activated Coagulation Time of Whole Blood.”
5. Weitz, Jeffrey I, and Jack Hirsh. “New Anticoagulant Drugs.: 2001; 95–107.
6. Rettie, Allan E, and Guoying Tai. 2006. “The Pharmacogenomics of Warfarin.”2006; 6(4):223–27.
7. Tew, Ben Yi Hong, Teresa B Otto-duessel, Maya Elix, Catherine Castro, Egbert He, Miaoling Wu, Xiwei Pal, Sumanta K Kalkum, Markus Jones, Jeremy O. “Vitamin K Epoxide Reductase Regulation of Androgen Receptor Activity.” 2017; 8(8):13818–31.
8. Yessica, Yustin, and Popi Septiani. 2022. “Analisis Transkriptomik Kaskade Koagulasi Darah Yang Dimodulasi Oleh Pisang Analisis Transkriptomik Kaskade Koagulasi Darah Yang Dimodulasi Oleh Pisang Tongka Langit ( Musa Troglodytarum ) Pada Usus Zebrafish ( Danio Rerio ) Yang Diinduksi Diabetes.” (February).
9. Tayjasanant, Thavatchai. “Analisis Nilai Clothing Time, Prothrombine Dan Activated Partial Thromboplastine Time Pada Remaja Obes.” 2008; 8013:75–85.
10. Maulida, Mentariasih, Diana Mayasari, and Fidha Rahmayani. “Pengaruh Rasio Kolesterol Total Terhadap High Density Lipoprotein ( HDL ) Pada Kejadian Stroke Iskemik The Influence of Total Cholesterol Ratio Against High Density Lipoprotein (HDL ) in The Incidence of Ischemic Stroke.” Majority 2018; 7(21):214–18.
11. Poller, Leon. 2001. “Clinical and Applied Thrombosis / Hemostasis.”
12. Link, Karl Paul. 1994. A Biographical Memoir by Robert H. Burris “1901—1978.”
13. Casper, Howard H Alstad, Arnold D Tacke, David B Johnson, Ladon J Lloyd, W Eugene. “Evaluation of Vitamin K 3 Feed Additive for Prevention of Sweet Clover Disease.” 1989; 19:116–19.
14. Timson, David J. 2015. “Dicoumarol : A Drug Which Hits at Least Two Very Different Targets in Vitamin.” (July).
15. Riveiro, M E Kimpe, N De Moglioni, A Vázquez, R Monczor, F Shayo, C Davio, C. “Coumarins : Old Compounds with Novel Promising Therapeutic Perspec- Tives.”: 2010; 1325–38.
16. Ningrum, Vitarani DA, Irine Dyah Widyastuti, Bacrie Sufriyanto Yusuf, and Wahyudin Dullah. “Senior Clinical Pharmacist at Sleman Regional Public Hospital, Sleman, Daerah Istimewa Yogyakarta, Indonesia 55514 3. Senior Clinical Pharmacist at Bethesda Hospital.” RESEARCH ARTICLE Indonesian Journal of Pharmacy Indonesian J Pharm 2020; 31(3):217–28.
17. Piatkov, Irina, Colin Rochester, Trudi Jones, and Steven Boyages. 2010. “Warfarin Toxicity and Individual Variability—Clinical Case.”2010; 2584–92.
18. Merck Index, An encyclopedia of chemicals and drugs, Notha Windholz IX Ed., Merck and Co. Inc., Rahway, N.J., U.S.A. page 1294 (1976).
19. Bentley and Driver's Textbook of Pharmaceutical Chemistry 8th Ed., L.M. Atherden, London, Oxford University Press (1969).
20. Whitlon, D. S., J. W. Suttie, and J. A. Sadowski. 1978. “Mechanism of Coumarin Action: Significance of Vitamin K Epoxide Reductase Inhibition.” Biochemistry 1978; 17(8):1371–77.
21. Ansell, Jack Hirsh, Jack Poller, Leon Bussey, Henry Jacobson, Alan Hijlek, Elaine. 2004. “The Pharmacology and Management of the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.” Chest 126(3 SUPPL.): 204S-233S.
22. Guo, Yingying Weller, Paul Farrell, Erin Cheung, Paul Fitch, Bill Clark, Douglas Wu, Shao Yong Wang, Jianmei Liao, Guochun Zhang, Zhaomei Allard, John Cheng, Janet Nguyen, Anh Jiang, Sharon Shafer, Steve Usuka, Jonathan Masjedizadeh, Mohammad Peltz, Gary. 2006. “In Silico Pharmacogenetics of Warfarin Metabolism.” Nature Biotechnology 2006; 24(5):531–36.
23. Gharagozloo, M. Kalantari, H. Rezaei, A. Maracy, M. R. Salehi, M. Bahador, A. Hassannejad, N. Narimani, M. Sanei, M. H. Bayat, B. Ghazanfari, H. “Clinical Study Immune-Mediated Cochleovestibular Disease.” Bratislavsk?? lek??rske listy 2015; 116(5):296–301.
24. Mcculloch, P, and W D George. 1989. “Warfarin Inhibits Metastasis of Mtln 3 Rat Affecting Primary Tumour Growth.” Cultures: 179–83.
25. Smith, G. F., Neubauer, B. L., Sundboom, J. L., Best, K. L., Goode, R. L., Tanzer L. R., Merriman, R. L., Frank, J. D., and Herrmann, R. G. Correlation of The In Vivo Anticoagulant, Antithrombotic and Antimetastatic. Thrombosis Research. 1988; 50(1):163-174.
26. Toomey, Jhon R. Abboud, M. A.Valocik, R. E. Koster, P.F.Burns-Kurtis, C. L.Pillariseri, T.M.Danoff, T. M.Erhardt, J. A. “A Comparison of the β-D-Xyloside, Odiparcil, to Warfarin in a Rat Model of Venous Thrombosis.” Journal of Thrombosis and Haemostasis 2006; 4(9):1989–96.
27. Beasley, James C. Clontz, Lindsay M. Rakowski, Allison Snow, Nathan P. VerCauteren, Kurt C. “Evaluation of a Warfarin Bait for Controlling Invasive Wild Pigs (Sus Scrofa).” Pest Management Science 2021; 77(7):3057–67.
28. Pharmacology, O P. 1978. “Of Ventilation by Warfarin1.”
29. Neubauer, B. L. et al. 1986. “Inhibitory Effect of Warfarin on the Metastasis of the PAIII Prostatic Adenocarcinoma in the Rat.” Journal of Urology 135(1): 163–66. http://dx.doi.org/10.1016/S0022-5347 (17)45554-6.
30. Foerch, Christian Arai, Ken Jin, Guang Park, Kyung Pil Pallast, Stefanie Van Leyen, Klaus Lo, Eng H. “Experimental Model of Warfarin-Associated Intracerebral Hemorrhage.” Stroke 2008; 39(12):3397–3404.
31. Krüger, Thilo Oelenberg, Stephan Kaesler, Nadine Schurgers, Leon J. Van De Sandt, Annette M. Boor, Peter Schlieper, Georg Brandenburg, Vincent M. Fekete, Bertalan C. Veulemans, Verena Ketteler, Markus Vermeer, Cees Jahnen-Dechent, Willi Floege, Jürgen Westenfeld, Ralf. 2013. “Warfarin Induces Cardiovascular Damage in Mice.” Arteriosclerosis, Thrombosis, and Vascular Biology 33(11): 2618–24.
32. Akdeniz, Universitas. 2014. “Diterjemahkan Dari Bahasa Turki Ke Bahasa Indonesia - Www.Onlinedoctranslator.Com.” : 101–25.
33. Colvin, H W, and W L E E Wang. 1974. “Toxic Effects of Warfarin in Rats Fed Different Diets Male Sprague-Dawley Rats , Weighing 250-300 g , Were Individually Caged in a Room Maintained at 22 ° C . One Group of 30 Rats Was Fed a Diet of Purina Laboratory Chow , l Hereafter Called ‘ Chow ’ ( Pr.” :1974; 337–48.
34. Alaydrus, H. 2015. “Mikroskopis Otak Dan Hati Pada Tikus Wistar Setelah Pemberian Warfarin Ld-50 Dan Ld-100.” 4(4): 933–47.
35. Howe, Andrew M., and Williams S. Webster.“Exposure of the Pregnant Rat to Warfarin and Vitamin K1: An Animal Model of Intraventricular Hemorrhage in the Fetus.” Teratology 1990; 42(4): 413–20.
36. Choonara, IA Malia, RG Haynes, BP Hay, CR Cholerton, S. Breckenridge, AM Preston, FE Park, BK. “The Relationship between Inhibition of Vitamin K1 2,3‐epoxide Reductase and Reduction of Clotting Factor Activity with Warfarin.” British Journal of Clinical Pharmacology 1988; 25(1): 1–7.
37. Krishnan, Subramanian, Namrata Chawla, Michael D. Ezekowitz, and Aldo J. Peixoto. “Warfarin Therapy and Systolic Hypertension in Men with Atrial Fibrillation.” American Journal of Hypertension 2005; 18(12):1592–99.
38. EKİZ, Mehmet, Latif DURAN, Hızır Ufuk AKDEMİR, and İskender AKSOY. “The Factors Associated With Bleeding in Patients Using Warfarin.” Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 2021; 23(3):482–91.
39. Finazzi, G. Brancaccio, V. Schinco, P. Wisloff, F. Musial, J. Baudo, F. Berrettini, M. Testa, S. D'Angelo, A. Tognoni, G. Barbui, T. Marchioli, Roberto. 2005. “A Randomized Clinical Trial of High-Intensity Warfarin vs. Conventional Antithrombotic Therapy for the Prevention of Recurrent Thrombosis in Patients with the Antiphospholipid Syndrome (WAPS).” Journal of Thrombosis and Haemostasis 3(5): 848–53.
40. Cheng, Alan Nazarian, Saman Brinker, Jeffrey A. Tompkins, Christine Spragg, David D. Leng, Charles T. Halperin, Henry Tandri, Harikrishna Sinha, Sunil K. Marine, Joseph E. Calkins, Hugh Tomaselli, Gordon F. Berger, Ronald D. Henrikson, Charles A.. 2011. “Continuation of Warfarin during Pacemaker or Implantable Cardioverter-Defibrillator Implantation: A Randomized Clinical Trial.” Heart Rhythm 2011; 8(4):536–40. http://dx.doi.org/10.1016/j.hrthm.2010.12.016.
41. Albert Schweitzer Hospital, Lambarene, Gabon, and Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.“Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation.” New England Journal of Medicine 2011; 365:687–96.
42. Mette, Hurlen, Abdelnoor, Mchael A Ål, P Mith, S An, J Rikssen, E. “The New England Journal of Medicine Warfarin, Aspirin, Or Both After Myocardial Infarction Background The Role of Antithrombotic Therapy In.” N Engl J Med 2002; 347(13):969–74. www.nejm.org.
43. Lotke, Paul A. Callaghan, John J. Dorr, Lawrence D. Engh, Gerard H. Hanssen, Arlen D. Healy, William L. Lachiewicz, Paul F. Lonner, Jess H. Nelson, Charles Ranawat, Chitranjan S. Ritter, Merrill A. Salvati, Eduarde A. Sculco, Thomas P. Thornhill, Thomas S. “Oral Direct Thrombin Inhibitor Ximelagatran Compared with Warfarin for the Prevention of Venous Thromboembolism after Total Knee Arthroplasty [9].” Journal of Bone and Joint Surgery - Series A 2006; 88(5):1163.
44. Al-Khatib, Sana M. Thomas, Laine Wallentin, Lars Lopes, Renato D. Gersh, Bernard Garcia, David Ezekowitz, Justin Alings, Marco Yang, Hongqui Alexander, John H. Flaker, Gregory Hanna, Michael Granger, Christopher B. “Outcomes of Apixaban vs. Warfarin by Type and Duration of Atrial Fibrillation: Results from the ARISTOTLE Trial.” European Heart Journal 2013; 34(31):2464–71.
45. Oates, A., P. R. Jackson, C. A. Austin, and K. S. Channer. “A New Regimen for Starting Warfarin Therapy in Out-Patients.” British Journal of Clinical Pharmacology 1998; 46(2):157–61.
46. Jeong, Jong-woo, Youngshin Song, and Tae-sung Koo. “Effects of Formulation Types on Pharmacodynamics of Warfarin in Patients with Cerebral Infarction and Dysphagia.” : 51–56.
47. Klang, Mark, Dennis Graham, and Veronica McLymont. “Warfarin Bioavailability with Feeding Tubes and Enteral Formula.” Journal of Parenteral and Enteral Nutrition 2010; 34(3): 300–304.
48. Sharley, Nicholas A., Annie M.C. Yu, and Desmond B. Williams.“Stability of Mixtures Formulated from Warfarin Tablets or Powder.” Journal of Pharmacy Practice and Research 2007; 37(2):95–97.
49. Schlatter, Joël, and Salvatore Cisternino. “Stability of Warfarin Sodium Flavoured Preservative-Free Oral Liquid Formulations.” European Journal of Hospital Pharmacy 2018; 25(e2): e98–101.
50. Abdallah, Siham, and Nourah A Al-abduwahed.“Availability and Stability of Crushed Warfarin Tablet in Different Solvents.” The Pharmaceutical and Chemical Journal 2016; 3(2):316–22.
Published
2022-08-14
How to Cite
Manao, T. A., Asra, R., & Chandra, B. (2022). Review: Drug Discovery and Development of Warfarin. Asian Journal of Pharmaceutical Research and Development, 10(4), 64–69. https://doi.org/10.22270/ajprd.v10i4.1158
Issue
Section
Review Articles
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