Real life Study on the Pharmacokinetic of Remdesivir in ICU patients admitted for Severe COVID‐19 Pneumonia

Corcione, Silvia; De Nicolò, Amedeo; Montrucchio, Giorgia; Scabini, Silvia; Avataneo, Valeria; Bonetto, Chiara; Mornese Pinna, Simone; Cusato, Jessica; Canta, Francesca; Urbino, Rosario; Di Perri, Giovanni; Brazzi, Luca; De Rosa, Francesco Giuseppe; D'Avolio, Antonio

Remdesivir is one of the most encouraging treatments against SARS‐CoV‐2 infection. After intravenous infusion, RDV is rapidly metabolized (T(1/2) 1h) 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 3 time points in nine ICU patients, through a validated 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), AUC(0–24), were < 0.24 ng/mL and 122.3 ng/ml, 2637,3 ng/mL and 157,8 ng/ml, 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 AUC(0–24) > 1560 ng*h/mL and 2230 ng*h/mL for RDV and GS‐441524, respectively. The mean T1/2 value for GS‐441524 was 26.3 h. Although the low number of patients, these data can represent an interesting preliminary report of the variability of RDV and GS‐441524 concentrations in real‐life ICU setting.