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Published on: August 30, 2018
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Model-based optimisation for teicoplanin dosing in patients undergoing maintenance haemodialysis.
Sebastian T Tandar1, Arnaud De Clercq2, Linda B S Aulin1
1Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Summary
Optimized teicoplanin dosing for haemodialysis patients improves treatment success. New dosing strategies and therapeutic drug monitoring (TDM) enhance teicoplanin
Area of Science:
- Pharmacokinetics and pharmacodynamics
- Infectious disease management
- Renal replacement therapy
Background:
- Patients on haemodialysis (HD) require effective treatment for Gram-positive infections, often with teicoplanin.
- Kidney replacement therapy significantly alters drug pharmacokinetics (PK), impacting treatment efficacy.
- Standard teicoplanin dosing may be suboptimal in HD patients due to altered PK.
Purpose of the Study:
- To characterize teicoplanin PK in patients undergoing maintenance HD.
- To identify predictors of interindividual variability in teicoplanin PK.
- To develop an evidence-based teicoplanin dosing strategy for HD patients.
Main Methods:
- Prospective observational PK study in 31 maintenance HD/haemodiafiltration patients.
- Development of a two-compartment population PK model incorporating dialyser flow.
- Monte Carlo simulations to assess probability of target attainment (PTA) for various dosing regimens and therapeutic drug monitoring (TDM).
Main Results:
- High teicoplanin clearance variability observed in the HD/HDF population.
- Standard thrice-weekly dosing achieved low PTA (<50%) after initial doses.
- Proposed fixed-dose regimen (1600 mg loading, 800 mg maintenance) significantly increased PTA (>60% in week 1).
- Cpredialysis-based TDM further improved PTA to >70%.
Conclusions:
- An optimized teicoplanin dosing strategy, including a loading dose and TDM, can maximize PTA in HD patients.
- High interindividual PK variability necessitates TDM for effective teicoplanin therapy in this population.
- Prospective validation of the proposed dosing strategy is recommended before clinical adoption.
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