COVID-19 TEDAVİSİNDE İLAÇ-İLAÇ ETKİLEŞİMLERİNİN FARMAKOKİNETİK AÇIDAN DEĞERLENDİRİLMESİ

Öz

Amaç: Çin'in Wuhan kentinde başlayan ve tüm dünyayı etkileyen COVID-19 pandemisi, bulaşıcılığı ve ölümcüllüğü benzersiz bir küresel mücadeleyi hala temsil etmektedir. COVID-19 hastalarının semptomları, hastalığın ciddiyetine göre farklılık gösterebilmektedir. Sağlık Bakanlığı Koronavirüs Araştırma Danışma Kurulu, COVID-19'un teşhisi, tedavisi ve kontrolü hakkında yayınladığı rapora göre ilaç kombinasyon tedavisi (hidroksiklorokin, lopinavir / ritonavir ve favipiravir) sağlık yetkilileri tarafından önerilmektedir. Çoğunlukla karaciğerde bulunan sitokrom P 450 enzimleri (CYP) tarafından metabolize edilen bu ilaçların diğer bazı ilaçlarla eş zamanlı kullanımları sonucu ilaç-ilaç etkileşimi olası bir durumdur. Biz bu derlemede COVID-19 tedavisinde kullanılan ilaçların özellikle metabolizma yolaklarını da belirterek farmakokinetik olarak ilaç-ilaç etkileşmelerini göstermeyi amaçladık.

Sonuç ve Tartışma: COVID-19 pandemisi dünya çapında sosyal hayatı, ekonomik ve finansal piyasaları olumsuz etkilemektedir. Uygun tedavi protokolleri büyük önem taşımaktadır. Ancak tedavi uygulamalarında ilaç-ilaç etkileşimlerinin göz önünde bulundurulması, hasta tedavisinde istenmeyen sonuçların oluşmasına engel olur.

Anahtar Kelimeler

• COVID 19
• ilaç-ilaç etkileşmeleri
• farmakokinetik
• CYP enzimleri

PHARMACOKINETIC EVALUATION OF DRUG-DRUG INTERACTIONS IN THE TREATMENT OF COVID-19

Öz

Objective: The COVID-19 pandemic, which started in Wuhan, China and affected the whole world, still represents a unique global challenge with its contagiousness and lethality. The symptoms of COVID-19 patients may differ depending on the severity of the disease. According to the report published by the Ministry of Health Coronavirus Research Advisory Board on the diagnosis, treatment and control of COVID-19, drug combination therapy (hydroxychloroquine, lopinavir / ritonavir and favipiravir) is recommended by health

authorities. Drug-drug interaction is a possible situation as a result of simultaneous use of these drugs, which are metabolized by cytochrome P 450 enzymes (CYP), which are mostly found in the liver, with some other drugs. In this review, we aimed to show the pharmacokinetic drug-drug interactions of the drugs used in the treatment of COVID-19, especially by indicating the metabolism pathways.

Result and Discussion: The COVID-19 pandemic adversely affects social life, economic and financial markets worldwide. Appropriate treatment protocols are of great importance but taking drug-drug interactions into account in treatment practices prevents unwanted results in patient treatment.

Anahtar Kelimeler

• COVID-19
• drug-drug interactions
• pharmacokinetic
• CYP enzymes

Kaynakça

1. 1. https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 (Erişim tarihi; 04.04.2020). WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020.
2. 2. https://crofsblogs.typepad.com/h5n1/2019/12/wuhan-municipal-health-commission-announces-pneumonia-epidemic.html (Erişim Tarihi; 11.02.2020). Wuhan Municipal Health and Health Commission’s Briefing on the Current Pneumonia Epidemic Situation in Our City. 2019.
3. 3. Zheng, Y. Y., Ma, Y. T., Zhang, J. Y., & Xie, X. (2020). COVID-19 and the cardiovascular system. Nature Reviews Cardiology, 17(5), 259-260.
4. 4. Gians, D., Ziogas, I. A., & Gianni, P. (2020). Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. Journal of Clinical Virology, 127, 104362.4.
5. 5. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it (Erişim Tarihi; 24.02.2020). Naming the Coronavirus Disease (COVID-19) and the virus that causes it.
6. 6. https://covid19.who.int (Erişim Tarihi; 12.02.2021)
7. 7. https://covid19.who.int/region/euro/country/tr (Erişim Tarihi; 12.02.2021)
8. 8. Dietz, L., Horve, P. F., Coil, D. A., Fretz, M., Eisen, J. A., & Van Den Wymelenberg, K. (2020). 2019 novel coronavirus (COVID-19) pandemic: built environment considerations to reduce transmission. Msystems, 5(2).

9. 9. Sriram, K., & Insel, P. A. (2020). A hypothesis for pathobiology and treatment of COVID‐19: The centrality of ACE1/ACE2 imbalance. British journal of pharmacology, 177(21), 4825-4844.
10. 10. Astuti, I. (2020). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(4), 407-412.
11. 11. Costela-Ruiz, V. J., Illescas-Montes, R., Puerta-Puerta, J. M., Ruiz, C., & Melguizo-Rodríguez, L. (2020). SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine & growth factor reviews.
12. 12. Wu, Z., & McGoogan, J. M. (2020). Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama, 323(13), 1239-1242.
13. 13. Jordan, R. E., Adab, P., & Cheng, K. K. (2020). Covid-19: risk factors for severe disease and death.
14. 14. Kalra, M. K., Homayounieh, F., Arru, C., Holmberg, O., & Vassileva, J. (2020). Chest CT practice and protocols for COVID-19 from radiation dose management perspective. European Radiology, 1-7.
15. 15. Ding, C., Feng, X., Chen, Y., Yuan, J., Yi, P., Li, Y., ... & Xu, K. (2020). Effect of corticosteroid therapy on the duration of SARS-CoV-2 clearance in patients with mild COVID-19: A retrospective cohort study. Infectious diseases and therapy, 9(4), 943-952.
16. 16. https://www.covid19treatmentguidelines.nih.gov/therapeutic-management/ (Erişim Tarihi; 11.02.2021 )
17. 17. https://www.covid19-druginteractions.org/ (Erişim Tarihi; 09.01.2020 )
18. 18. https://khgmstokyonetimidb.saglik.gov.tr/TR-64698/covid--19-tedavisinde-kullanilan-ilaclar---ilac-etkilesimleri.html (Erişim Tarihi; 06.01.2020 )
19. 19. Mehra, M. R., Desai, S. S., Kuy, S., Henry, T. D., & Patel, A. N. (2020). Cardiovascular disease, drug therapy, and mortality in Covid-19. New England Journal of Medicine, 382(25), e102.
20. 20. Projean, D., Baune, B., Farinotti, R., Flinois, J. P., Beaune, P., Taburet, A. M., & Ducharme, J. (2003). In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation. Drug Metabolism and Disposition, 31(6), 748-754.
21. 21. Paniri, A., Hosseini, M. M., Rasoulinejad, A., & Akhavan-Niaki, H. (2020). Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: role of CYP450 isoforms and epigenetic modulations. European Journal of Pharmacology, 886, 173454.
22. 22. Hodge, C., Marra, F., Marzolini, C., Boyle, A., Gibbons, S., Siccardi, M., ... & Khoo, S. (2020). Drug interactions: a review of the unseen danger of experimental COVID-19 therapies. Journal of Antimicrobial Chemotherapy, 75(12), 3417-3424.
23. 23. O'Horo, J. C. (2020). Chloroquine. Elsevier.
24. 24. Lemaitre, F., Solas, C., Grégoire, M., Lagarce, L., Elens, L., Polard, E., ... & French Society of Pharmacology, Therapeutics (SFPT), the International Association of Therapeutic Drug Monitoring, Clinical Toxicology (IATDMCT). (2020). Potential drug–drug interactions associated with drugs currently proposed for COVID‐19 treatment in patients receiving other treatments. Fundamental & Clinical Pharmacology, 34(5), 530-547.
25. 25. https://www.who.int/news/item/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19 (Erişim Tarihi; 06.08.2020 )
26. 26. Chandwani, A., & Shuter, J. (2008). Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Therapeutics and clinical risk management, 4(5), 1023.
27. 27. Chen, C., Huang, J., Cheng, Z., Wu, J., Chen, S., Zhang, Y., ... & Wang, X. (2020). Favipiravir versus arbidol for COVID-19: a randomized clinical trial. MedRxiv.
28. 28. Cai, Q., Yang, M., Liu, D., Chen, J., Shu, D., Xia, J., ... & Liu, L. (2020). Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering, 6(10), 1192-1198.
29. 29. Coomes, E. A., & Haghbayan, H. (2020). Favipiravir, an antiviral for COVID-19? Journal of Antimicrobial Chemotherapy, 75(7), 2013-2014.
30. 30. Doi, Y., Hibino, M., Hase, R., Yamamoto, M., Kasamatsu, Y., Hirose, M., ... & Kondo, M. (2020). A prospective, randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19. Antimicrobial agents and chemotherapy, 64(12).
31. 31. Agrawal, U., Raju, R., & Udwadia, Z. F. (2020). Favipiravir: A new and emerging antiviral option in COVID-19. Medical Journal Armed Forces India.
32. 32. Irie, K., Nakagawa, A., Fujita, H., Tamura, R., Eto, M., Ikesue, H., ... & Hashida, T. (2020). Pharmacokinetics of Favipiravir in critically ill patients with COVID‐19. Clinical and translational science, 13(5), 880-885.
33. 33. Rubin, D., Chan-Tack, K., Farley, J., & Sherwat, A. (2020). FDA approval of remdesivir—a step in the right direction. New England Journal of Medicine, 383(27), 2598-2600.
34. 34. Norrie, J. D. (2020). Remdesivir for COVID-19: challenges of underpowered studies. The Lancet, 395(10236), 1525-1527.
35. 35. Wang, L. Y., Cui, J. J., Ouyang, Q. Y., Zhan, Y., Guo, C. X., & Yin, J. Y. (2020). Remdesivir and COVID-19. The Lancet, 396(10256), 953-954. 36. Beigel, J. H., Tomashek, K. M., Dodd, L. E., Mehta, A. K., Zingman, B. S., Kalil, A. C., ... & Lane, H. C. (2020). Remdesivir for the treatment of Covid-19—preliminary report. The New England journal of medicine.
36. 37. Yang, K. (2020). What do we know about remdesivir drug interactions? Clinical and translational science, 13(5), 842-844.
37. 38. McCreary, E. K., & Pogue, J. M. (2020, April). Coronavirus disease 2019 treatment: a review of early and emerging options. In Open forum infectious diseases (Vol. 7, No. 4, p. ofaa105). US: Oxford University Press.
38. 39. https://www.covid19‐druginteractions.org (Erişim Tarihi; 04.05.2020). Liverpool Drug Interactions Group University of Liverpool. COVID‐19 drug interactions.
39. 40. Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet, 395(10229), 1033-1034.
40. 41. Tang, C., Wang, Y., Lv, H., Guan, Z., & Gu, J. (2020). Caution against corticosteroid-based COVID-19 treatment. The Lancet, 395(10239), 1759-1760.
41. 42. RECOVERY Collaborative Group. (2020). Dexamethasone in hospitalized patients with Covid-19—preliminary report. New England Journal of Medicine.
42. 43. Kanazu, T., Yamaguchi, Y., Okamura, N., Baba, T., & Koike, M. (2004). Model for the drug–drug interaction responsible for CYP3A enzyme inhibition. I: evaluation of cynomolgus monkeys as surrogates for humans. Xenobiotica, 34(5), 391-402.
43. 44. Wong, D. D., Longenecker, R. G., Liepman, M., Baker, S., & LaVergne, M. (1985). Phenytoin-dexamethasone: a possible drug-drug interaction. JAMA, 254(15), 2062-2063.
44. 45. Rayman, G. E. R. R. Y., Lumb, A. N., Kennon, B., Cottrell, C., Nagi, D., Page, E., ... & Stewart, R. (2021). Dexamethasone therapy in COVID‐19 patients: implications and guidance for the management of blood glucose in people with and without diabetes. Diabetic Medicine, 38(1), e14378.
45. 46. Le, R. Q., Li, L., Yuan, W., Shord, S. S., Nie, L., Habtemariam, B. A., ... & Pazdur, R. (2018). FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell‐induced severe or life‐threatening cytokine release syndrome. The oncologist, 23(8), 943.
46. 47. Hermine, O., Mariette, X., Tharaux, P. L., Resche-Rigon, M., Porcher, R., Ravaud, P., ... & Korganow, A. S. (2021). Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA internal medicine, 181(1), 32-40.
47. 48. Salama, C., Han, J., Yau, L., Reiss, W. G., Kramer, B., Neidhart, J. D., ... & Mohan, S. V. (2021). Tocilizumab in patients hospitalized with Covid-19 pneumonia. New England Journal of Medicine, 384(1), 20-30.
48. 49. Salvarani, C., Dolci, G., Massari, M., Merlo, D. F., Cavuto, S., Savoldi, L., ... & Costantini, M. (2021). Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA internal medicine, 181(1), 24-31.
49. 50. Zhang, S., Li, L., Shen, A., Chen, Y., & Qi, Z. (2020). Rational use of tocilizumab in the treatment of novel coronavirus pneumonia. Clinical drug investigation, 40(6), 511-518.
50. 51. Lescure, F. X., Honda, H., Fowler, R. A., Lazar, J. S., Shi, G., Wung, P., ... & Hagino, O. (2021). Sarilumab treatment of hospitalised patients with severe or critical COVID-19: a multinational, randomised, adaptive, phase 3, double-blind, placebo-controlled trial. medRxiv.
51. 52. Balkhair, A., Al-Zakwani, I., Al Busaidi, M., Al-Khirbash, A., Al Mubaihsi, S., BaTaher, H., ... & Balkhair, O. (2021). Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: results of a prospective, open-label, interventional study. International Journal of Infectious Diseases, 103, 288-296.
52. 53. Pasin, L., Cavalli, G., Navalesi, P., Sella, N., Landoni, G., Yavorovskiy, A. G., ... & Monti, G. (2021). Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies. European journal of internal medicine.
53. 54. Hung, I. F. N., Lung, K. C., Tso, E. Y. K., Liu, R., Chung, T. W. H., Chu, M. Y., ... & Yuen, K. Y. (2020). Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. The Lancet, 395(10238), 1695-1704.
54. 55. Yuan, J., Li, M., Yu, Y., Lee, T. Y., Lv, G., Han, B., ... & Lu, Z. K. (2021). Pharmacotherapy Management for COVID-19 and Cardiac Safety: A Data Mining Approach for Pharmacovigilance Evidence from the FDA Adverse Event Reporting System (FAERS). Drugs-Real World Outcomes, 1-10.