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Journal of Pharmaceutical Research

Article

Journal of Pharmaceutical Research

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

Original Article

Pharmacokinetic Interaction of Favipiravir with Citalopram and Pioglitazone

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-19International Journal of Infectious Diseases2021;102:501508. Available from: https://doi.org/10.1016/j.ijid.2020.10.069
  2. Perlman S. Another Decade, Another CoronavirusNew England Journal of Medicine2020;382(8):760762. 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-7052002;46(4):977981. 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 VirusAntimicrobial Agents and Chemotherapy2005;49(3):981986. 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 infectionsAntiviral Research2009;82(3):95102. 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 inhibitorAntiviral Research2013;100(2):446454. 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 TrialsClinical Pharmacokinetics2016;55(8):907923. Available from: https://doi.org/10.1007/s40262-015-0364-1
  8. 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 InfectionThe Journal of Infectious Diseases2020;221(10):16881698. Available from: https://doi.org/10.1093/infdis/jiz656
  9. Sangkuhl K, Klein TE, Altman RB. PharmGKB summary: citalopram pharmacokinetics pathwayPharmacogenet Genomics2011;21(11):769772. Available from: https://doi.org/10.1097%2FFPC.0b013e328346063f
  10. 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 BeyondFrontiers in Pharmacology2018;9:1093. Available from: https://doi.org/10.3389%2Ffphar.2018.01093
  11. Hwang I, Kim Y, Yoo H, Jang IJ, Yu KS, Lee S. Pharmacokinetic/Pharmacodynamic Interaction between Evogliptin and Pioglitazone in Healthy Male SubjectsDrug Des Devel Therb2020;14:44934502. Available from: https://doi.org/10.2147/dddt.s275336
  12. Obach RS, Huynh P, Allen MC, Beedham C. Human Liver Aldehyde Oxidase: Inhibition by 239 DrugsThe Journal of Clinical Pharmacology2004;44(1):719. Available from: https://doi.org/10.1177/0091270003260336
  13. Saha SK, Chowdhury AA, Bachar SC. Pharmacokinetics study of Pioglitazone (30 mg) tablets in healthy volunteersDhaka University Journal of Pharmaceutical Sciences2014;13(2):181186. Available from: file:///C:/Users/PRABAKAR/Downloads/15020.pdf
  14. Zhang Y, Huo M, Zhou J, Xie S, Pksolver. An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft ExcelComputer methods and programs in biomedicine2010;99(3):306314. Available from: https://doi.org/10.1016/j.cmpb.2010.01.007
  15. 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 repaglinideEuropean Journal of Clinical Pharmacology2006;62(3):217223. Available from: https://doi.org/10.1007/s00228-005-0093-8
  16. Manitpisitkul P, Curtin CR, Shalayda K, Wang SSS, Ford L, Heald D. Pharmacokinetic interactions between topiramate and pioglitazone and metforminEpilepsy Research2014;108(9):15191532. Available from: https://doi.org/10.1016/j.eplepsyres.2014.08.013
  17. Mishima E, Anzai N, Miyazaki M, Abe T. Uric Acid Elevation by Favipiravir, an Antiviral DrugThe Tohoku Journal of Experimental Medicine2020;251(2):8790. Available from: https://doi.org/10.1620/tjem.251.87
  18. Jaakkola T, Backman JT, Neuvonen M, Neuvonen P. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazoneClinical Pharmacology & Therapeutics2005;77(5):404414. Available from: https://doi.org/10.1016/j.clpt.2004.12.266
  19. Itkonen MK, Tornio A, Neuvonen M, Neuvonen PJ, Niemi M, Backman JT. Clopidogrel Markedly Increases Plasma Concentrations of CYP2C8 Substrate PioglitazoneDrug Metabolism and Disposition2016;44(8):13641371. Available from: https://doi.org/10.1124/dmd.116.070375
  20. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic ratsSaudi Medical Journal2021;42(2):151160. Available from: https://doi.org/10.15537/smj.2021.2.25695
  21. Levin TT, Cortes-Ladino A, Weiss M, Palomba ML. Life-threatening serotonin toxicity due to a citalopram-fluconazole drug interaction: case reports and discussionGeneral Hospital Psychiatry2008;30(4):372377. Available from: https://doi.org/10.1016/j.genhosppsych.2008.03.008
  22. Anderson LL, Doohan PT, Oldfield L, Kevin RC, ArnoldjcBerger M, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young PeopleJ Clin Psychopharmacol2021;41(5):525533. 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/

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