Real-life study on the pharmacokinetic of remdesivir in ICU patients admitted for severe COVID-19 pneumonia.

Abstract

Remdesivir is one of the most encouraging treatments against SARS‐CoV‐2 infection. After intravenous infusion, RDV is rapidly metabolized (t 1/2 = 1 h) within the cells to its active adenosine triphosphate analogue form (GS‐443902) and then it can be found in plasma in its nucleoside analogue form (GS‐441524). In this real‐life study, we describe the remdesivir and GS‐441524 concentrations at three time points in nine ICU patients, through a validated ultra‐high‐performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) method. The observed data confirmed the very rapid conversion of RDV to its metabolite and the quite long half‐life of GS‐441524. The mean C min, C max and AUC0–24, were < 0.24 ng/mL and 122.3 ng/mL, 2637.3 ng/mL and 157.8 ng/mL, and 5171.2 ng*h/mL and 3676.5 ng*h/ml, respectively, for RDV and GS‐441524. Three out of nine patients achieved a C max > 2610 ng/mL and 140 ng/mL and AUC0–24 > 1560 ng*h/mL and 2230 ng*h/mL for RDV and GS‐441524, respectively. The mean t 1/2 value for GS‐441524 was 26.3 h. Despite the low number of patients, these data can represent an interesting preliminary report on the variability of RDV and GS‐441524 concentrations in a real‐life ICU setting.