Population pharmacokinetics of prophylactic cefoxitin in elective bariatric surgery patients: A prospective monocentric study.
bariatric surgery
cefoxitin
continuous infusion.
obesity
pharmacokinetics
surgical prophylaxis
Journal
Anaesthesia, critical care & pain medicine
ISSN: 2352-5568
Titre abrégé: Anaesth Crit Care Pain Med
Pays: France
ID NLM: 101652401
Informations de publication
Date de publication:
15 Mar 2024
15 Mar 2024
Historique:
received:
24
10
2023
revised:
19
02
2024
accepted:
12
03
2024
medline:
18
3
2024
pubmed:
18
3
2024
entrez:
17
3
2024
Statut:
aheadofprint
Résumé
This study describes the population pharmacokinetics of cefoxitin in obese patients undergoing elective bariatric surgery and evaluates different dosing regimens for achievement of pre-defined target exposures. Serial blood samples were collected during surgery with relevant clinical data. Total serum cefoxitin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. The cefoxitin unbound fraction (fu) was estimated. Dosing simulations were performed to ascertain the probability of target attainment (PTA) to achieve cefoxitin fu above minimum inhibitory concentrations (MIC) from surgical incision to wound closure. Fractional target attainment (FTA) was calculated against MIC distributions of common pathogens. A total of 123 obese patients (median BMI 44.3 kg/m Intermittent dosing regimens resulted in optimal FTAs against susceptible MIC distributions of S. aureus and E. coli when simulating with 50% cefoxitin protein binding. Continuous infusion of cefoxitin may improve FTA regardless of protein binding. Registration on ClinicalTrials.gov, NCT03306290.
Sections du résumé
BACKGROUND
BACKGROUND
This study describes the population pharmacokinetics of cefoxitin in obese patients undergoing elective bariatric surgery and evaluates different dosing regimens for achievement of pre-defined target exposures.
METHODS
METHODS
Serial blood samples were collected during surgery with relevant clinical data. Total serum cefoxitin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. The cefoxitin unbound fraction (fu) was estimated. Dosing simulations were performed to ascertain the probability of target attainment (PTA) to achieve cefoxitin fu above minimum inhibitory concentrations (MIC) from surgical incision to wound closure. Fractional target attainment (FTA) was calculated against MIC distributions of common pathogens.
RESULTS
RESULTS
A total of 123 obese patients (median BMI 44.3 kg/m
CONCLUSION
CONCLUSIONS
Intermittent dosing regimens resulted in optimal FTAs against susceptible MIC distributions of S. aureus and E. coli when simulating with 50% cefoxitin protein binding. Continuous infusion of cefoxitin may improve FTA regardless of protein binding.
STUDY REGISTRATION
BACKGROUND
Registration on ClinicalTrials.gov, NCT03306290.
Identifiants
pubmed: 38494157
pii: S2352-5568(24)00034-1
doi: 10.1016/j.accpm.2024.101376
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT03306290']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101376Informations de copyright
Copyright © 2024. Published by Elsevier Masson SAS.