Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C-Reactive Protein in Hospitalized Patients With Gram-Positive Infections.

Abstract

Teicoplanin is an antibiotic agent used for the treatment of Gram-positive infections. The clinical benefit of teicoplanin is associated with its blood concentrations, but the optimal dosing regimen is not yet known. To explore the optimal individual dosing regimen, we performed a population pharmacokinetic (PK) and pharmacodynamic (PD) analysis targeting a large-scale population, including patients with a wide range of ages, body weights, and renal functions. The PK of teicoplanin was described with a 2-compartment model, and the PD of C-reactive protein (CRP) concentrations was described with a turnover maximum inhibition model. The elimination half-life of teicoplanin calculated from the final estimated parameters was 169hours, and renal function was a significant covariate of teicoplanin clearance. The teicoplanin concentration producing 50% of the maximum inhibition of CRP production was estimated to be 2.66mg/L. The minimum concentration of teicoplanin in patients with higher loading doses (15mg/kg) reached the target range (15-30mg/L) with a probability of >50% in the dosing simulation. We described the influence of body size, body composition, and renal function on the PK of teicoplanin. The population PKPD model of teicoplanin and CRP in this study should provide useful information for development of a dosing strategy including the sequential clinical benefit of teicoplanin.