Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

Abstract

The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 μg/ml for mild to moderate infections and a trough concentration target of >15 μg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).

Keywords: cardiogenic shock; extracorporeal membrane oxygenation; pharmacokinetics; population pharmacokinetics; teicoplanin.

Copyright © 2017 American Society for Microbiology.

Figures

FIG 1

Goodness-of-fit plots of the final population pharmacokinetic model for teicoplanin in 10 patients who received venoarterial extracorporeal membrane oxygenation. Observed teicoplanin concentrations versus population predicted concentrations (A) and individual predicted concentrations (B) and conditional weighted residuals versus population predicted concentrations (C) and time (D) are shown.

FIG 2

Visual predictive check of the final population pharmacokinetic model for teicoplanin in 10 patients during venoarterial extracorporeal membrane oxygenation (A) and after discontinuation of venoarterial extracorporeal membrane oxygenation (B). Open circles, observed teicoplanin concentrations; solid line, the median; lower and upper dashed lines, 5th and 95th percentiles of the simulated data, respectively.