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Journal of Pharmaceutical Research

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Pharmacokinetic Interaction of Favipiravir with Citalopram and Pioglitazone
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Journal of Pharmaceutical Research

DOI: 10.18579/jopcr/v21i4.28

Year: 2022, Volume: 21, Issue: 4, Pages: 136-143

Original Article

Pharmacokinetic Interaction of Favipiravir with Citalopram and Pioglitazone

Zeliha Keskin Alkaç​ ✉ 1 , Dilan Aşkın Özek 2 , Hande Yüce 3 , Fatih Ahmet Korkak 1 , Sümeyye Aslan 4 , Neşe Başak Türkmen 3 , Songül Ünüvar 3

 
1 Pharmacology and Toxicology Department, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
2 Department of Pharmacy Services, Kovancilar Vocational School, Firat University, Elazig, Turkey
3 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Inonu University, Malatya, Turkey
4 Department of Pharmaceutical Toxicology, Institute of Health Sciences, Inonu University, Malatya, Turkey

Corresponding author ✉: [email protected]

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

The current study's objective was to investigate the interactions of favipiravir with pioglitazone and citalopram. 25 Spraque-Dawley female rats were used in the study. Rats in groups 1 and 4 were given pioglitazone (1 mg/kg/day) for 7 days and rats in groups 2 and 5 were given citalopram (1.5 mg/kg/day) for 7 days. Rats in groups 3, 4, and 5 were given a loading dose (50 mg/kg) on the 6th day of the study and a maintenance dose of favipiravir (30 mg/kg) on the 7th day of the study. After the last drug administration, blood samples were taken from the rats at 15, 30, and 45 minutes, and 1, 2, 4, 6, and 8 hours. Plasma concentrations of drugs were determined by high-performance liquid chromatography (HPLC). The aldehyde oxidase (AO) and xanthine oxidase (XO) activities in liver tissues were determined by enzyme-linked immunosorbent assay (ELISA). Pioglitazone changed the pharmacokinetics of favipiravir and increased t1/2, AUC, MRT and Cl values. Favipiravir did not affect the pharmacokinetics of pioglitazone at a steady state. When used together, favipiravir significantly decreased Cl while increasing citalopram's t1/2, AUC, and MRT values. While citalopram increased the t1/2, Cmax, AUMC, and Cl values of favipiravir, it decreasing the AUC value. Pharmacokinetic drug interactions have been determined between favipiravir and AO substrates or modulators. It is thought that if the results obtained are supported by human studies, it will guide the concomitant use of these drugs in the clinic to prevent the occurrence of adverse reactions.

 

Keywords: Drug-drug interaction, Favipiravir, Pioglitazone, Citalopram, Aldehyde oxidase

References

  1. Joshi S, Parkar J, Ansari A, Vora A, Talwar D, Tiwaskar M, et al. Role of favipiravir in the treatment of COVID-19. International Journal of Infectious Diseases. 2021;102:501–508. Available from: https://doi.org/10.1016/j.ijid.2020.10.069
  2. Perlman S. Another Decade, Another Coronavirus. New England Journal of Medicine. 2020;382(8):760–762. Available from: https://doi.org/10.1056/NEJMe2001126
  3. Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, et al. vitro and in vivo activities of anti-influenza virus compound T-705. 2002;46(4):977–981. Available from: https://doi.org/10.1128/aac.46.4.977-981.2002
  4. Furuta Y, Takahashi K, Kuno-Maekawa M, Sangawa H, Uehara S, Kozaki K, et al. Mechanism of Action of T-705 against Influenza Virus. Antimicrobial Agents and Chemotherapy. 2005;49(3):981–986. Available from: https://doi.org/10.1128/aac.49.3.981-986.2005
  5. Furuta Y, Takahashi K, Shiraki K, Sakamoto K, Smee DF, Barnard DL, et al. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Research. 2009;82(3):95–102. Available from: https://doi.org/10.1016/j.antiviral.2009.02.198
  6. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Research. 2013;100(2):446–454. Available from: https://doi.org/10.1016%2Fj.antiviral.2013.09.015
  7. Madelain V, Nguyen THT, Olivo A, Lamballerie XD, Guedj J, Taburet AMM, et al. Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials. Clinical Pharmacokinetics. 2016;55(8):907–923. Available from: https://doi.org/10.1007/s40262-015-0364-1
  9. Wang Y, Fan G, Salam A, Horby P, Hayden FG, Chen C, et al. Comparative Effectiveness of Combined Favipiravir and Oseltamivir Therapy Versus Oseltamivir Monotherapy in Critically Ill Patients With Influenza Virus Infection. The Journal of Infectious Diseases. 2020;221(10):1688–1698. Available from: https://doi.org/10.1093/infdis/jiz656
  10. Sangkuhl K, Klein TE, Altman RB. PharmGKB summary: citalopram pharmacokinetics pathway. Pharmacogenet Genomics. 2011;21(11):769–772. Available from: https://doi.org/10.1097%2FFPC.0b013e328346063f
  12. Devchand PR, Liu T, Altman RB, Fitzgerald GA, Schadt EE. The Pioglitazone Trek via Human PPAR Gamma: From Discovery to a Medicine at the FDA and Beyond. Frontiers in Pharmacology. 2018;9:1093. Available from: https://doi.org/10.3389%2Ffphar.2018.01093
  13. Hwang I, Kim Y, Yoo H, Jang IJ, Yu KS, Lee S. Pharmacokinetic/Pharmacodynamic Interaction between Evogliptin and Pioglitazone in Healthy Male Subjects. Drug Des Devel Therb. 2020;14:4493–4502. Available from: https://doi.org/10.2147/dddt.s275336
  14. Obach RS, Huynh P, Allen MC, Beedham C. Human Liver Aldehyde Oxidase: Inhibition by 239 Drugs. The Journal of Clinical Pharmacology. 2004;44(1):7–19. Available from: https://doi.org/10.1177/0091270003260336
  17. Saha SK, Chowdhury AA, Bachar SC. Pharmacokinetics study of Pioglitazone (30 mg) tablets in healthy volunteers. Dhaka University Journal of Pharmaceutical Sciences. 2014;13(2):181–186. Available from: file:///C:/Users/PRABAKAR/Downloads/15020.pdf
  18. Zhang Y, Huo M, Zhou J, Xie S, Pksolver. An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Computer methods and programs in biomedicine. 2010;99(3):306–314. Available from: https://doi.org/10.1016/j.cmpb.2010.01.007
  19. Kajosaari LI, Jaakkola T, Neuvonen PJ, Backman JT. Pioglitazone, an in vitro inhibitor of CYP2C8 and CYP3A4, does not increase the plasma concentrations of the CYP2C8 and CYP3A4 substrate repaglinide. European Journal of Clinical Pharmacology. 2006;62(3):217–223. Available from: https://doi.org/10.1007/s00228-005-0093-8
  20. Manitpisitkul P, Curtin CR, Shalayda K, Wang SSS, Ford L, Heald D. Pharmacokinetic interactions between topiramate and pioglitazone and metformin. Epilepsy Research. 2014;108(9):1519–1532. Available from: https://doi.org/10.1016/j.eplepsyres.2014.08.013
  21. Mishima E, Anzai N, Miyazaki M, Abe T. Uric Acid Elevation by Favipiravir, an Antiviral Drug. The Tohoku Journal of Experimental Medicine. 2020;251(2):87–90. Available from: https://doi.org/10.1620/tjem.251.87
  22. Jaakkola T, Backman JT, Neuvonen M, Neuvonen P. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clinical Pharmacology & Therapeutics. 2005;77(5):404–414. Available from: https://doi.org/10.1016/j.clpt.2004.12.266
  23. Itkonen MK, Tornio A, Neuvonen M, Neuvonen PJ, Niemi M, Backman JT. Clopidogrel Markedly Increases Plasma Concentrations of CYP2C8 Substrate Pioglitazone. Drug Metabolism and Disposition. 2016;44(8):1364–1371. Available from: https://doi.org/10.1124/dmd.116.070375
  24. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats. Saudi Medical Journal. 2021;42(2):151–160. Available from: https://doi.org/10.15537/smj.2021.2.25695
  25. Levin TT, Cortes-Ladino A, Weiss M, Palomba ML. Life-threatening serotonin toxicity due to a citalopram-fluconazole drug interaction: case reports and discussion. General Hospital Psychiatry. 2008;30(4):372–377. Available from: https://doi.org/10.1016/j.genhosppsych.2008.03.008
  26. Anderson LL, Doohan PT, Oldfield L, Kevin RC, Arnoldjc, Berger M, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. J Clin Psychopharmacol. 2021;41(5):525–533. Available from: https://doi.org/10.1097/jcp.0000000000001427

Copyright

© 2022 Published by Krupanidhi College of Pharmacy. This is an open-access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) 

  • 04 March 2023

Year: 2022, Volume: 21, Issue: 4


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