Population pharmacokinetics of unbound ceftriaxone in a critically ill population.
Int J Clin Pharmacol Ther
; 60(9): 373-383, 2022 Sep.
Article
in En
| MEDLINE
| ID: mdl-35861497
ABSTRACT
OBJECTIVE:
To develop a reliable 2-compartment population pharmacokinetic (PK) model for unbound ceftriaxone in a critically ill population and determine an optimal dosing regimen. MATERIALS ANDMETHODS:
This was a prospective, single-center, observational study of critically ill patients treated with ceftriaxone. Unbound serum ceftriaxone concentrations were measured using validated ultrafiltration and ultra-performance liquid chromatography-tandem mass spectrometry. PK analysis and dosing simulations were performed using an iterative 2-stage Bayesian fitting procedure and Monte Carlo simulations. The PK/pharmacodynamics (PD) target was attained when unbound serum ceftriaxone concentrations exceeded 4 times the minimum inhibitory concentration (MIC) for ≥ 60% of the dosing interval (ƒT>4xMIC ≥ 60%).RESULTS:
91 patients were enrolled, and 173 unbound ceftriaxone concentrations were acquired. The population PK parameter estimates were hepatic clearance 5.2 ± 0.9 L/h/1.85m2, the unbound renal clearance of ceftriaxone divided by the creatinine clearance 0.61 ± 0.24, lean body mass corrected volume of distribution of the central compartment 0.82 ± 0.21 L/kg, and intercompartmental distribution rate constant from central to peripheral compartment 0.18 ± 0.08 h-1. Dosing simulations predicted ƒT>4 mg/L of 88% (95% CI 69 - 100%) for 2,000 mg ceftriaxone once daily and ƒT>4 mg/L of 100% (95% CI 100 - 100%) both for 1,000 mg twice daily and continuous infusion of 2,000 mg daily.CONCLUSION:
We developed a reliable population PK model for unbound ceftriaxone in a critically ill population. Dosing simulations revealed ƒT>4 mg/L ≥ 60% for 1,000 mg twice daily and 2,000 mg once daily or by continuous infusion.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ceftriaxone
/
Critical Illness
Type of study:
Health_economic_evaluation
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Int J Clin Pharmacol Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2022
Document type:
Article