Purpose: To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin.
Methods: This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations.
Results: The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (V_c), inter-compartmental clearance (Q) and volumes of the peripheral compartments (V_p) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m²) to attain target trough concentration (C_min, PTA 52.8%). When eGFR > 30 mL/min/1.73 m², increasing dose and the administration times of loading doses were the preferred options to achieve target C_min based on the renal function and types of infection.
Conclusion: The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.
Keywords: teicoplanin, pharmacokinetics, Monte Carlo simulation, intensive care unit, renal function