Pharmacokinetics and Target Attainment of Teicoplanin: A Systematic Review.

Abstract

Background and objective: Teicoplanin is a glycopeptide antibiotic used to treat severe Gram-positive infections. This systematic review provides a comprehensive overview of the current knowledge on the pharmacokinetics of teicoplanin across the entire population, with the aim to identify gaps in the existing literature, prioritise pharmacokinetic research, and support optimal dosing strategies.

Methods: A systematic literature search of the MEDLINE, Embase, Web of Science, and Scopus databases was conducted. Articles published until 1 October 2024 were identified as eligible when they included a pharmacokinetic analysis of teicoplanin. Relevant pharmacokinetic data were extracted from all included articles. Allometric scaling was carried out for reported values of clearance (CL) and volume of distribution (Vd) to an individual of 70 kg. Articles were categorised into eight subgroups. A qualitative assessment of the included studies was conducted using the clinical pharmacokinetic statement checklist.

Results: In total, 85 articles were included in this review. Pharmacokinetic data for 186 healthy volunteers, 130 neonates, 788 children, 1434 adult patients, 48 older adults (≥ 65 years), 674 critically ill patients, 33 patients with impaired renal function, and 159 patients with extracorporeal elimination techniques were extracted for a total of 3452 subjects. Unbound concentrations were assessed in 7.1% of the articles. The Vd_scaled ranged from 1.5 to 583 L/70 kg. The CL_scaled ranged from 0.0073 to 6.38 L/h/70 kg. Covariates on drug disposition were identified in 55.3% of studies, 65.6% of which identified a relationship between renal function and CL. Target attainment was described in 42.4% of articles. Dosing recommendations were provided in 61.2% of all studies. Studies had an average quality score of 69.9% ± standard deviation 15.7.

Conclusion: Individual dosing strategies based on renal function need to be developed, particularly in patients with immature or impaired renal function, using state-of-the art pharmacokinetic/pharmacodynamic modelling approaches. Since teicoplanin is highly plasma protein bound and it is suggested that total concentrations cannot be easily translated to unbound concentrations, future research should also include the measurement of unbound concentrations for pharmacokinetic and target attainment evaluation.

Trial registration: Prospectively registered in PROSPERO.

Trial registration number: CRD42023483334. Registration date: 03/12/2023.