Exploration for the effect of renal function and renal replacement therapy on pharmacokinetics of remdesivir and GS-441524 in patients with COVID-19: A limited case series

Abstract

Remdesivir, an antiviral agent for the treatment of coronavirus disease 2019 (COVID-19), is metabolized intracellularly, with these metabolites eliminated predominantly in urine. Because of a lack of safety and pharmacokinetic (PK) data, remdesivir is not currently recommended for patients with estimated glomerular filtration rate less than 30 ml/min/1.73 m(2) and those on hemodialysis. This study evaluated the PKs of remdesivir and its metabolite, GS-441524, in patients with COVID-19 who were and were not receiving renal replacement therapy (RRT). This study enrolled two patients with normal renal function, two with impaired renal function not receiving RRT, two receiving continuous RRT (CRRT), and three undergoing intermittent hemodialysis (IHD). Patients were administered 200 mg remdesivir on the first day, followed by 100 mg/day for 5-10 days. Serial blood samples were collected for PK analysis, and PK parameters were assessed by a noncompartmental method. Systemic exposure to remdesivir was higher in patients with impaired renal function and those receiving CRRT than in patients with normal renal function, but was similar in patients undergoing IHD and those with normal renal function. By contrast, systemic exposure to GS-441524 was highest in patients undergoing IHD, followed by patients with impaired renal function and those receiving CRRT, and lowest in patients with normal renal function. The PK profiles of remdesivir and GS-441524 varied according to renal function and RRT. The impact of PK changes of remdesivir and its metabolite on safety and efficacy should be considered when administering remdesivir to patients with COVID-19 with renal impairment.