Optimization of Teicoplanin Dosing Regimen in Adult Patients Using an Externally Evaluated Population Pharmacokinetic Model.

Abstract

Background: This study aimed to identify population pharmacokinetic models suitable for optimizing individualized teicoplanin dosing regimens in adult Chinese patients.

Methods: PubMed and Web of Science were searched for teicoplanin population pharmacokinetic models developed for the general adult population. Patient data used for the external evaluation, including demographics, teicoplanin-related information (administration and blood concentration), and laboratory test values, were collected from the Beijing Electric Power Hospital. External evaluation was performed using the Nonlinear Mixed-Effects Modeling software. Models with excellent predictive abilities were identified, and Monte Carlo simulations were conducted.

Results: A total of 66 teicoplanin concentrations used for external evaluation were obtained from 62 patients. The model built by Ogami et al performed excellently, with a bias of -7.56% and inaccuracy of 26.28%. The model consisted of the following parameters: clearance (L/h) = (0.379 + 0.211 × creatinine clearance/100) × (total body weight/70)0.75; volume (V) 1 (L) = 38.2 × (fat-free mass/70); Q (L/h) = 2.42 × (total body weight/70)0.75; V2 (L) = 106 × (fat-free mass/70). The model was subsequently used in Monte Carlo simulations (n = 1000). For general infections (minimum plasma concentration [Cmin] = 10-15 mg/L), the loading dose (LD) and maintenance dose (MD) of teicoplanin should be at least 400 mg to achieve the target concentration. For endocarditis or severe infections, where a target concentration (Cmin = 15-30 mg/L) is required, LD should be at least 800 mg. Alternatively, the LD and MD of teicoplanin should be at least 600 mg to achieve desired therapeutic levels.

Conclusions: By combining external evaluations using Nonlinear Mixed-Effects Modeling with Monte Carlo simulations, the model developed by Ogami et al was identified as the most suitable for guiding clinical dosing under different pathophysiological conditions.