Optimizing cloxacillin prophylaxis in hip and knee arthroplasty based on population pharmacokinetics of unbound plasma concentrations

Key Points

• To characterize the pharmacokinetics of unbound cloxacillin in total hip and knee arthroplasties and explore alternative dosing regimens.
• Analyzed plasma concentrations of cloxacillin from 200 patients undergoing THA or TKA.
• Administered intravenous cloxacillin doses of 2 g pre-surgery and at two intervals after.
• Conducted non-linear mixed-effects modeling to develop a pharmacokinetic model.
• Explored alternative dosing regimens using Monte Carlo simulations.
• A two-compartment model described the data, indicating significant covariates like eGFR and body weight.
• 13% of patients had unbound cloxacillin levels < 2 mg/L at the end of surgery.
• Current regimens showed that 18–22% of patients failed to maintain plasma levels ≥ 2 mg/L during surgery.
• A continuous 1 g/h infusion after a 1 g loading dose could achieve target levels in over 99% of patients.