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

Remdesivir is one of the most encouraging treatments against SARS-CoV-2 infection. After intravenous infusion, RDV is rapidly metabolized (T1/2 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 Cmin , Cmax , AUC0-24 , 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 Cmax > 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 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.