Model-based optimisation for teicoplanin dosing in patients undergoing maintenance haemodialysis

Patients on haemodialysis (HD) are commonly treated with teicoplanin for Gram-positive infections. Kidney replacement therapy is known to alter drug pharmacokinetics (PK), which impacts treatment success. This study aimed to characterize teicoplanin PK, explore potential covariate predictors for interindividual variability, and derive an evidence-based dosing strategy for patients undergoing maintenance HD.

A monocentric prospective observational PK study in patients undergoing maintenance HD was conducted at the Ghent University Hospital and its low care at the General Hospital Aalst. Total and unbound teicoplanin concentrations were used to inform the development of a teicoplanin population PK model. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for predialysis teicoplanin concentrations (C_predialysis) of 20-50 mg/L across dosing regimens. The impact of administration of a predialysis dose and therapeutic drug monitoring (TDM) on target attainment was evaluated.

This study included 31 patients on teicoplanin therapy undergoing maintenance HD or haemodiafiltration (HDF). The final model consists of a two-compartment population PK model with a semimechanistic dialyser flow. High clearance variability was observed across the cohort. The standard 12 mg/kg thrice-weekly regimen achieved PTA of 13.6% (HD) and 6.8% (HDF) after the first dose, which increased to approximately 50% with subsequent doses. A fixed-dose regimen was proposed with a single 1600 mg loading dose, followed by an 800 mg maintenance dose (1200 mg for 3-day interdialytic periods). The proposed dosing regimen increased PTA to 71.7% (HD) and 66.9% (HDF) after the first loading dose, with week 1 averages of 61.1% and 59.9%, respectively. C_predialysis-based TDM further improved PTA to >70% in both groups.

This study proposed an optimized dosing strategy to maximize PTA in patients undergoing maintenance HD, although prospective validation is recommended before clinical implementation. Furthermore, the estimated high clearance variability underscores the need for TDM in teicoplanin dosing for this population.