Abstract

Objective: There is limited information on favipiravir pharmacokinetics in critically ill patients and no studies on pharmacokinetics in patients with moderate and severe kidney dysfunction. The aim was to determine favipiravir pharmacokinetics (oral, 1,600 mg, q12h on day 1, then 600 mg, q12h for 4 days) in critically ill COVID-19 patients with kidney dysfunction and to compare those with observations reported in healthy adults.
Materials and methods: In a descriptive study, blood samples taken from patients meeting the relevant criteria (estimated glomerular filtration rate < 60 mL/min) were collected and analyzed. Analysis of blood samples was done by high performance liquid chromatography (HPLC), and the maximal concentration (C_max), the time of maximal concentration (t_max), half-life (T_1/2) and area under the curve (AUC_0–12h) of favipiravir were calculated (WinNonlin) and compared to reported data in healthy subjects after first administration.
Results: Based on analysis of samples collected in 7 patients, the C_max (29.99 vs. 64.5 µg/mL) of favipiravir was decreased, T_1/2 (5.8 vs. 4.8 hours) longer, t_max delayed, while total exposure was lower (AUC_0–12: 192.53 vs. 446.09 μg/mL) compared to reported data in healthy subjects after first administration. Exposure remained lower up to day 5.
Conclusion: In patients with kidney dysfunction related to COVID-19, favipiravir did not reach the expected exposure. This may be due to poorer and delayed absorption, and subsequent altered disposition. Population pharmacokinetic and mechanistic studies are needed to better explore the relevant covariates and to determine the optimal dose in these patients, as this drug is likely of relevance for other indications.

Author Details

Authors

• Nursel Sürmelioğlu¹
• Esra Demirtürk²
• Nazire Ateş Ayhan³
• Aysun Özel Yeşilyurt³
• Sinem Bayrakçi³
• Mustafa Sinan Kaynak⁴
• Ezgi Özyılmaz³
• Karel Allegaert^{5, 6, 7}

Departments

• ¹ Department of Clinical Pharmacy,
• ² Department of Pharmaceutical Technology, Faculty of Pharmacy,
• ³ Department of Intensive Care Unit, Faculty of Medicine, Çukurova University, Adana,
• ⁴ Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey,
• ⁵ Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium,
• ⁶ Department of Clinical Pharmacy, Erasmus Medical Center, Rotterdam, the Netherlands, and
• ⁷ Department of Development and Regeneration, KU Leuven, Leuven, Belgium

Address

Nursel Sürmelioğlu, Associate Professor, PhD
Department of Clinical Pharmacy
Faculty of Pharmacy, Çukurova University
Adana, Turkey
Email: [email protected]

Citation