Favipiravir pharmacokinetics in COVID-19 patients with moderate to severe kidney dysfunction: Lessons learned

• Published in: International journal of clinical pharmacology and therapeutics Vol. 62; no. 8; pp. 345 - 352
• Main Authors: Sürmelioğlu, Nursel, Demirtürk, Esra, Ayhan, Nazire Ateş, Yeşilyurt, Aysun Özel, Bayrakçi, Sinem, Kaynak, Mustafa Sinan, Özyılmaz, Ezgi, Allegaert, Karel
• Format: Journal Article
• Language: English
• Published: Germany Dustri - Verlag Dr. Karl Feistle GmbH & Co. KG 01.08.2024
• Subjects: Adult; Aged; Amides - pharmacokinetics; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Area Under Curve; COVID-19; COVID-19 - complications; COVID-19 Drug Treatment; Critical Illness; Female; Glomerular Filtration Rate; Half-Life; Humans; Male; Middle Aged; Pharmacokinetics; Pyrazines - administration & dosage; Pyrazines - pharmacokinetics; Renal Insufficiency - complications; Renal Insufficiency - metabolism; SARS-CoV-2; Severity of Illness Index
• ISSN: 0946-1965
• DOI: 10.5414/CP204496

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. 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 ), the time of maximal concentration (t ), half-life (T ) and area under the curve (AUC ) of favipiravir were calculated (WinNonlin) and compared to reported data in healthy subjects after first administration. Based on analysis of samples collected in 7 patients, the C (29.99 vs. 64.5 µg/mL) of favipiravir was decreased, T (5.8 vs. 4.8 hours) longer, t delayed, while total exposure was lower (AUC : 192.53 vs. 446.09 μg/mL) compared to reported data in healthy subjects after first administration. Exposure remained lower up to day 5. 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.