Population pharmacokinetics and probability of target attainment of ertapenem administered by subcutaneous or intravenous route in patients with bone and joint infection

Background: Ertapenem is a therapeutic option in patients with Gram-negative bone and joint infection (BJI).The subcutaneous (sc) route of administration is convenient in the outpatient setting and has shown favourablepharmacokinetics (PK), but available data on ertapenem are limited.Objectives: To perform population PK analysis and pharmacokinetic/pharmacodynamic (PK/PD) simulation ofertapenemadministered by the intravenous (iv) or sc route to patients with BJI.Patients and methods: This was a retrospective analysis of PK data collected in patients with BJI who received ivor sc ertapenem. Measured ertapenem concentrations were analysed with a non-parametric population approach.Then, simulations were performed based on the final model to investigate the influence of ertapenemroute of administration, dosage and renal function on the probability of achieving a pharmacodynamic (PD) target,defined as the percentage of time for which free plasma concentrations of ertapenem remained above theMIC (fT>MIC) of 40%.Results: Forty-six PK profiles (13 with iv and 33 with sc ertapenem) with a total of 133 concentrations from31 subjects were available for the analysis. A two-compartment model with linear sc absorption and linear eliminationbest fitted the data. Creatinine clearance was found to significantly influence ertapenem plasma clearance.Simulations showed that twice daily dosing, sc administration and renal impairment were associated withan increase in fT>MIC and target attainment.Conclusions: Our results indicate that 1 g of ertapenemadministered twice daily, by the iv or sc route, may optimizeertapenem exposure and achievement of PK/PD targets in patients with BJI.