Remdesivir (RDV) pharmacokinetics in the PICU

ABSTRACT

INTRODUCTION: Remdesivir (RDV) is an antiviral agent with in-vitro activity against SARS-CoV-2 that has been used during the COVID-19 pandemic. Dosing strategies for pediatric and adolescent patients have primarily been extrapolated from adult dosing recommendations and, to date, there is a lack of pharmacokinetic (PK) data of RDV in this patient population. METHODS: Electronic medical record review of patients receiving RDV with concurrent therapeutic drug monitoring (TDM). RDV and GS-441524 concentrations were determined by LC-MS/MS methodology. RESULTS: 3 patients (2 female1 male) met inclusion criteria and contributed 74 samples for determination of RDV and the active GS-441524 metabolite. The median age was 16 yrs (IQR 15.5-16 yrs) with a median weight of 76.4 kg (IQR 74.9-94.3kg). Patient #1 received ECMO support for the duration of RDV therapy. Patients #1 and 2 received RDV for 10 days with levels obtained daily. Patient #3 received RDV for 5 days with levels obtained daily. For all patients, mean RDV exposures, range 272-893 ng/mL were below the mean exposures reported in the RDV investigators brochure, 2900-7800 ng/mL. Patient #1 received ECMO and RDV exposures did not appear impacted by ECMO when compared with patients #2 and #3 that did not receive ECMO. For all patients, mean GS-441524 exposures, range 109-258 ng/mL, were similar to the mean exposures reported in the RDV investigators brochure, range 69-184 ng/mL. Similarly, the GS-441524 exposure did not appear to be affected by ECMO. Patients #1 and #2 did not appear to have any observable adverse events as a result of receiving RDV. Patient #3 experienced and increase in ALT >5x ULN which resulted in having RDV discontinued. All 3 patients experienced clinical resolution. CONCLUSIONS: These are the first PK data of RDV in critically ill adolescent patients. These preliminary data suggest using adult dosing recommendations in adolescent patients result in RDV exposures below mean values demonstrated in adults with similar exposures of GS-441524 which could be a result of rapid conversion of RDV to GS- 441524 with delayed elimination in the setting of critical illness. Additional PK data of RDV in the critically ill pediatric population is warranted.