Pharmacokinetics of <scp>SARS</scp>‐<scp>CoV</scp>‐2 <scp>RNA</scp> Polymerase Inhibitor Remdesivir in Participants With Moderate and Severe Hepatic Impairment

Remdesivir is an RNA polymerase inhibitor of severe acute respiratory syndrome coronavirus 2 administered intravenously (IV) that is approved for the treatment of coronavirus disease 2019 in hospitalized and nonhospitalized patients. The clinical dosing regimen is a single loading dose of 200 mg on Day 1 followed by once-daily maintenance doses of 100 mg from Day 2, for a total duration of up to 10 days. The prodrug, remdesivir, undergoes metabolic activation inside the cell to form the intracellular active metabolite (GS-443902) along with two plasma metabolites (GS-704277 and GS-441524). The pharmacokinetics and safety of a single IV 100-mg dose of remdesivir were evaluated in a Phase 1, open-label, multicenter study in participants with moderate (n = 10) or severe (n = 6) hepatic impairment (Child-Pugh-Turcotte Class B or C, respectively) and participants with normal liver function (n = 16). Compared with the normal hepatic function group, plasma exposures (geometric least squares mean ratios of area under the concentration-time curve extrapolated to infinity and maximum concentration) of remdesivir, GS-704277, and GS-441524 were similar in the moderate hepatic impairment group and up to 1.56-fold, 2.41-fold, and 1.48-fold higher, respectively, in the severe hepatic impairment group. Remdesivir was generally safe and well tolerated in hepatically impaired individuals, and the modest exposure increases of remdesivir and its metabolites were not associated with adverse events. Based on these findings, no dose adjustment of remdesivir is recommended for patients with mild, moderate, or severe hepatic impairment.