TY - JOUR
T1 - Population pharmacokinetics of dexamethasone in critically ill COVID-19 patients
T2 - Does inflammation play a role?
AU - Li, Letao
AU - Sassen, Sebastiaan
AU - Hunfeld, Nicole
AU - Smeets, Tim
AU - Ewoldt, Tim
AU - van den Berg, Sjoerd A.A.
AU - Koch, Birgit
AU - Endeman, Henrik
N1 - Funding Information:
Letao Li acknowledge the China Scholarship Council for the support by State Scholarship Fund No. 201908500113 .
Publisher Copyright:
© 2023 The Authors
PY - 2023/12
Y1 - 2023/12
N2 - Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.
UR - https://www.scopus.com/pages/publications/85166775490
U2 - 10.1016/j.jcrc.2023.154395
DO - 10.1016/j.jcrc.2023.154395
M3 - Article
C2 - 37542750
AN - SCOPUS:85166775490
SN - 0883-9441
VL - 78
JO - Journal of Critical Care
JF - Journal of Critical Care
M1 - 154395
ER -