Clinical pharmacokinetics · 2026
Population Pharmacokinetics of Intravenous Cefuroxime in Plasma and Bone of Patients with Prosthetic Joint Infection: Is There Room for Dose Optimization?
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de Waard Gerbert Coen, Zhao Qiaolin, Veltman Ewout S, van Oldenrijk Jakob, Bos P Koen, Bahmany Soma, Muller Anouk, Preijers Tim, Koch Birgit C P
Аннотация
BACKGROUND AND OBJECTIVE: Prosthetic joint infections are serious infections that require perioperative antibiotic prophylaxis. Cefuroxime may be used as prophylaxis, and this study aims to evaluate the current dosing regimen to prevent infection during the perioperative period by performing population pharmacokinetic (PK) analysis of plasma and bone in patients with prosthetic joint infection (PJI).
METHODS: Both plasma and bone samples were taken perioperatively and analyzed using NONMEM. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) in both plasma and bone of various dosing regimens.
RESULTS: A total of 44 plasma and 38 bone samples from 25 patients were included. The median bone concentration at 30-60 min after administration was 18.2 (9.9-25.3) mg/L and the bone-to-plasma ratio was 0.269 (interquartile range [IQR] 0.179-0.269), while the median bone concentration at 90-120 min after administration was 12.6 (5.9-18.6) mg/L and the bone-to-plasma ratio was 0.125 (IQR 0.073-0.160). A two-compartment model with allometric scaling and proportional errors best described plasma and bone concentrations. Only estimated glomerular filtration rate could partly explain the inter-individual variability (IIV) of clearance (CL). A single dose of 1500 mg cefuroxime failed to maintain bone concentrations above target concentrations for Staphylococcus aureus beyond 3.83 h post administration.
CONCLUSION: A population PK model was developed to characterize the disposition of cefuroxime in both plasma and bone compartments. Although adequate cefuroxime bone penetration within 1 h was observed in patients with PJI with rapid clearance, simulations predicted less optimal levels of cefuroxime after 3.5 h. The clinical implications need to be researched and confirmed.
METHODS: Both plasma and bone samples were taken perioperatively and analyzed using NONMEM. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) in both plasma and bone of various dosing regimens.
RESULTS: A total of 44 plasma and 38 bone samples from 25 patients were included. The median bone concentration at 30-60 min after administration was 18.2 (9.9-25.3) mg/L and the bone-to-plasma ratio was 0.269 (interquartile range [IQR] 0.179-0.269), while the median bone concentration at 90-120 min after administration was 12.6 (5.9-18.6) mg/L and the bone-to-plasma ratio was 0.125 (IQR 0.073-0.160). A two-compartment model with allometric scaling and proportional errors best described plasma and bone concentrations. Only estimated glomerular filtration rate could partly explain the inter-individual variability (IIV) of clearance (CL). A single dose of 1500 mg cefuroxime failed to maintain bone concentrations above target concentrations for Staphylococcus aureus beyond 3.83 h post administration.
CONCLUSION: A population PK model was developed to characterize the disposition of cefuroxime in both plasma and bone compartments. Although adequate cefuroxime bone penetration within 1 h was observed in patients with PJI with rapid clearance, simulations predicted less optimal levels of cefuroxime after 3.5 h. The clinical implications need to be researched and confirmed.