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

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.