Pharmacokinetics of baricitinib in critically ill COVID-19 patients.
Baricitinib
COVID-19
Critical care
Pharmacokinetics
Journal
Clinical biochemistry
ISSN: 1873-2933
Titre abrégé: Clin Biochem
Pays: United States
ID NLM: 0133660
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
22
03
2023
revised:
12
06
2023
accepted:
15
06
2023
medline:
7
8
2023
pubmed:
24
6
2023
entrez:
23
6
2023
Statut:
ppublish
Résumé
The use of the selective Janus Kinase 1/2 inhibitor baricitinib has shown a survival benefit in mechanically ventilated COVID-19 patients but this is not without adverse drug reactions. Although critically ill patients are at risk of altered drug exposure, data on baricitinib pharmacokinetics (PK) are scarce. This study describes real-life baricitinib plasma exposure in critically ill COVID-19 patients. This retrospective observational study was conducted in critically ill patients with COVID-19 treated with baricitinib 4 mg/day. Plasma concentrations were measured at predose (C0), 1 h (C1) and 3 h (C3) after the drug intake. PK and area under the curve (AUC) were estimated using non-compartmental pharmacokinetic analysis. Seven patients contributed to 22 baricitinib plasma concentration measurements after a median [range] of 3 days [2-3] of treatment. Median baricitinib plasma concentrations were 2.2 ng/mL [1.4-8.0], 24.0 ng/mL [4.9-37.3] and 14.1 ng/mL [8.3-15.1] for trough (C0), C1 and C3 concentrations respectively. The median AUC 0-24 h was 188.8 ng.h/mL [141.3-236.3]. No difference was observed in C0 and C1 when comparing patients according to body mass index < or > 30. The patient with the lowest glomerular filtration rate (74 mL/min) had the highest baricitinib trough concentration. Overall, 2 patients had liver function test perturbation and both of them had atypical PK with delayed time to reach maximum concentration. High inter-patient variability and relatively low baricitinib trough concentrations and AUC were observed in critically ill COVID-19 patients receiving the usual dosage of 4 mg/day. This preliminary study encourages further exploration of the concentration-effect relationship of baricitinib in this clinical context.
Sections du résumé
BACKGROUND
BACKGROUND
The use of the selective Janus Kinase 1/2 inhibitor baricitinib has shown a survival benefit in mechanically ventilated COVID-19 patients but this is not without adverse drug reactions. Although critically ill patients are at risk of altered drug exposure, data on baricitinib pharmacokinetics (PK) are scarce. This study describes real-life baricitinib plasma exposure in critically ill COVID-19 patients.
METHODS
METHODS
This retrospective observational study was conducted in critically ill patients with COVID-19 treated with baricitinib 4 mg/day. Plasma concentrations were measured at predose (C0), 1 h (C1) and 3 h (C3) after the drug intake. PK and area under the curve (AUC) were estimated using non-compartmental pharmacokinetic analysis.
RESULTS
RESULTS
Seven patients contributed to 22 baricitinib plasma concentration measurements after a median [range] of 3 days [2-3] of treatment. Median baricitinib plasma concentrations were 2.2 ng/mL [1.4-8.0], 24.0 ng/mL [4.9-37.3] and 14.1 ng/mL [8.3-15.1] for trough (C0), C1 and C3 concentrations respectively. The median AUC 0-24 h was 188.8 ng.h/mL [141.3-236.3]. No difference was observed in C0 and C1 when comparing patients according to body mass index < or > 30. The patient with the lowest glomerular filtration rate (74 mL/min) had the highest baricitinib trough concentration. Overall, 2 patients had liver function test perturbation and both of them had atypical PK with delayed time to reach maximum concentration.
CONCLUSION
CONCLUSIONS
High inter-patient variability and relatively low baricitinib trough concentrations and AUC were observed in critically ill COVID-19 patients receiving the usual dosage of 4 mg/day. This preliminary study encourages further exploration of the concentration-effect relationship of baricitinib in this clinical context.
Identifiants
pubmed: 37353137
pii: S0009-9120(23)00129-7
doi: 10.1016/j.clinbiochem.2023.110601
pmc: PMC10284613
pii:
doi:
Substances chimiques
baricitinib
ISP4442I3Y
Azetidines
0
Types de publication
Observational Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110601Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.