Scholarlink

Background and Objective <p>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).</p> Methods <p>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.</p> Results <p>A total of 44 plasma and 38 bone samples from 25 patients were included. The median bone concentration at 30–60&#xa0;min after administration was 18.2 (9.9–25.3)&#xa0;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&#xa0;min after administration was 12.6 (5.9–18.6)&#xa0;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&#xa0;mg cefuroxime failed to maintain bone concentrations above target concentrations for <i>Staphylococcus aureus</i> beyond 3.83&#xa0;h post administration.</p> Conclusion <p>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&#xa0;h was observed in patients with PJI with rapid clearance, simulations predicted less optimal levels of cefuroxime after 3.5&#xa0;h. The clinical implications need to be researched and confirmed.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Population Pharmacokinetics of Intravenous Cefuroxime in Plasma and Bone of Patients with Prosthetic Joint Infection: Is There Room for Dose Optimization?

  • 期刊论文

  • 发表日期：

    2026年1月4日

查看全文
  • Gerbert Coen de Waard,
  • Qiaolin Zhao,
  • Ewout S. Veltman,
  • Jakob van Oldenrijk,
  • P. Koen Bos,
  • Soma Bahmany,
  • Anouk Muller,
  • Tim Preijers,
  • Birgit C. P. Koch

摘要

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.