Pharmacokinetic Modeling and Dosing Simulations of Temocillin in Children With Urinary Tract Infections
Xin Liu, Perrin Ngougni Pokem, Marc Hainaut, Christine Ferreiro, Catherine Adler, Jason A. Roberts, Françoise Van BambekeBackground:
Temocillin, active against most extended-spectrum β-lactamases (ESBL)-producing
Methods:
Eligible patients contributed 1–2 blood samples collected at different time points, providing coverage of the dosing interval through an ethically acceptable sparse sampling strategy. Total and unbound temocillin plasma concentrations were quantified using high-performance liquid chromatography–tandem mass spectrometry, and data were used for pharmacokinetic modeling. Probabilities of target attainment were calculated using Monte Carlo simulation.
Results:
Pediatric patients (6–34 months) hospitalized with urinary tract infection received temocillin at a dose of 25 mg/kg twice daily. Thirty unbound and 33 total plasma concentrations collected from 30 patients were available for analysis. A 1-compartment structural model including nonlinear protein binding was supported. Population pharmacokinetic estimates fell within the corresponding 95% confidence intervals and were consistent with bootstrap medians, supporting model stability. Clearance and volume of distribution were estimated at 2.81 L/h and 10.3 L, respectively. Interindividual variability of clearance was determined to be 21.2% in the population. Modeling predicted that the studied regimen would provide a >90% probability of target attainment against organisms with minimum inhibitory concentration (MIC) ≤2 mg/L when targeting 40% of the dosing interval with free-drug concentrations above the MIC (40% fT>MIC).
Conclusion:
Although sparse sampling limits parameter precision, characterization of interindividual variability, and covariate evaluation, these data may serve as an exploratory reference to inform preliminary dosing considerations in this pediatric population.