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Pharmacokinetic characterization of favipiravir in patients with COVID-19 and patient outcome
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  • Rezzan Gülhan,
  • Emel Eryüksel,
  • Medine Gülçebi Idriz Oglu,
  • Yekta Çulpan,
  • Aylin Toplu,
  • Derya Kocakaya,
  • Elif Tükenmez Tigen,
  • Buket Ertürk Şengel,
  • Uluhan Sili,
  • Sehnaz Olgun Yildizeli,
  • Baran Balcan,
  • Abdullah Elçi,
  • Cenk Bulut,
  • Atila Karaalp,
  • Hasan Yananli,
  • Abdullah Güner,
  • Mustafa Hatipoglu,
  • Sait Karakurt,
  • Volkan Korten,
  • Neville Ratnaraj,
  • Philip Patsalos,
  • Pinar Ay,
  • Filiz Yilmaz Onat
Rezzan Gülhan
Marmara University School of Medicine
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Emel Eryüksel
Marmara University School of Medicine
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Medine Gülçebi Idriz Oglu
Marmara University School of Medicine
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Yekta Çulpan
Marmara University School of Medicine
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Aylin Toplu
Marmara University School of Medicine
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Derya Kocakaya
Marmara University School of Medicine
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Elif Tükenmez Tigen
Marmara University School of Medicine
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Buket Ertürk Şengel
Marmara University School of Medicine
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Uluhan Sili
Marmara University School of Medicine
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Sehnaz Olgun Yildizeli
Marmara University School of Medicine
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Baran Balcan
Marmara University School of Medicine
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Abdullah Elçi
Istanbul Provincial Health Directorate
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Cenk Bulut
Istanbul Provincial Health Directorate
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Atila Karaalp
Marmara University School of Medicine
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Hasan Yananli
Marmara University School of Medicine
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Abdullah Güner
Istanbul Health Directorate
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Mustafa Hatipoglu
Istanbul Health Directorate
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Sait Karakurt
Marmara University School of Medicine
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Volkan Korten
Marmara University School of Medicine
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Neville Ratnaraj
University College London Queen Square Institute of Neurology
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Philip Patsalos
University College London Queen Square Institute of Neurology
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Pinar Ay
Marmara University School of Medicine
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Filiz Yilmaz Onat
Marmara University School of Medicine
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Abstract

Favipiravir is one of the repurposed antiviral medications for the treatment of SARS-CoV-2 infection. Since the dosing regimen is a prominent factor for the success of the antiviral therapy, this prospective observational study aimed to characterize the pharmacokinetic characteristics of favipiravir in COVID-19 patients. Adult patients (n=21) hospitalized for mild to moderate COVID-19 with a positive RT-PCR test, and assigned for favipiravir treatment were included. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a 1200 mg/day maintenance dose. Serial blood samples were collected on Day-2 and Day-4 of the therapy. Laboratory findings of the patients and in-hospital mortality were assessed. Favipiravir concentrations exhibited high variations and a significant decrease during the treatment of COVID-19. The median favipiravir trough concentration (C0-trough) on Day-2 was 21.26 µg/mL whereas it decreased significantly to 1.61 µg/mL on Day-4, the area under the concentration versus time curve decreased from 345.6 µg.h/mL to 108.6 µg.h/mL, respectively. Gender seems significant to affect favipiravir concentrations. Day-2-C0-trough of female patients was significantly higher than male patients. Of the 5 patients that died, 4 were male with a significant increase in ferritin levels from Day-0 to Day-5 compared to surviving patients. In addition, there was a significant decrease in D-dimer and CRP levels in the surviving patients. Our findings indicate that favipiravir concentrations show significant changes during the treatment of COVID-19. Therapeutic drug monitoring may best guide dose adjustments in patients that do not respond to treatment with favipiravir.

Peer review status:IN REVISION

16 Jun 2021Submitted to British Journal of Clinical Pharmacology
19 Jun 2021Assigned to Editor
19 Jun 2021Submission Checks Completed
01 Jul 2021Reviewer(s) Assigned
14 Jul 2021Review(s) Completed, Editorial Evaluation Pending
31 Jul 2021Editorial Decision: Revise Major