Publication date: Dec 01, 2023
The aim of this study is to design a population pharmacokinetic study to gain a deeper understanding of the pharmacokinetics of dexamethasone in critically ill COVID-19 patients in order to identify relevant covariates that can be used to personalize dosing regimens. Blood samples from critically ill patients receiving fixed-dose intravenous dexamethasone (6 mg/day) for the treatment of COVID-19 were sampled in a retrospective pilot study. The data were analyzed using Nonlinear Mixed Effects Modeling (NONMEM) software for population pharmacokinetic analysis and clinically relevant covariates were selected and evaluated. A total of 51 dexamethasone samples from 18 patients were analyzed and a two-compartment model fit the data best. The mean population estimates were 2. 85 L/h (inter-individual-variability 62. 9%) for clearance, 15. 4 L for the central volume of distribution, 12. 3 L for the peripheral volume of distribution and 2. 1 L/h for the inter-compartmental distribution clearance. The covariate analysis showed a significant negative correlation between dexamethasone clearance and CRP. Dexamethasone PK parameters in ICU COVID patients were substantially different from those from non-ICU non-COVID patients, and inflammation may play an important role in dexamethasone exposure. This finding suggests that fixed-dose dexamethasone over several days may not be appropriate for ICU COVID patients.