Tigecycline population pharmacokinetics in patients with community- or hospital-acquired pneumonia

Abstract

Tigecycline is a new-generation of tetracycline (glycylcyclines) and is active in vitro against bacteria that possess any of the classical genes that confer tetracycline resistance through ribosomal protection or efflux pumps. Herein, tigecycline disposition in patients with community- or hospital-acquired pneumonia was described using a population pharmacokinetic model. Additionally, the influence of covariates, such as body surface area, severity of illness, and clinical laboratory measures, on tigecycline disposition was evaluated. An intravenous loading dose of 100 mg was followed by 50 mg of tigecycline every 12 h. The final population pharmacokinetic model was a two-compartment model with linear elimination and with a relationship between tigecycline clearance and body surface area and creatinine clearance. The model was parameterized using total clearance (CL), the volume of the central compartment, distributional clearance from the central to the peripheral compartment, and volumes of distribution at steady state. Relationships between body surface area and creatinine clearance were identified as significant predictors of interindividual variability on CL. This model will serve as the basis for estimating tigecycline exposure for pharmacokinetic-pharmacodynamic analyses for efficacy and safety among patients with community- or hospital-acquired pneumonia.

FIG. 1.

Scatter plot of observed versus individual predicted tigecycline concentrations for the final population model for patients with either community- or hospital-acquired pneumonia (A). Scatter plot of individual weighted residuals versus individual predicted tigecycline concentrations for the final population model (B). Note that the solid line represents the line of identity. OBS, observed; PRED, predicted.

FIG. 2.

Frequency distribution histograms of mean parameter estimates from analysis of the 50 bootstrap data sets. Note that the vertical line represents the mean estimate from the analysis of the original data set.