Pharmacokinetics and target attainment of teicoplanin : a systematic review

Background 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 (PK) of teicoplanin across the entire population, with the aim to identify gaps in the existing literature, prioritise PK 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 October 1, 2024, were identified as eligible when they included a PK analysis of teicoplanin. Relevant PK data was extracted from all included articles. Allometric scaling was carried out for reported values of clearance (CL) and volume of distribution (Vd). Articles were categorised into eight subgroups. A qualitative assessment of the included studies was conducted using the clinical pharmacokinetic statement checklist. Results Eighty-five articles were included in this review. PK data of 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 was extracted for a total of 3452 subjects. Unbound concentrations were assessed in 9.4% of the articles. The median scaled Vd was 60.20 L/70 kg (IQR 39.32 - 84.00). The median scaled CL was 0.77 L/h/70 kg (IQR 0.55 - 1.06). 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. Different targets were used across the studies. Unbound teicoplanin PK was investigated in 9.4% of studies. Dosing recommendations were provided in 61.2% of all studies. Studies had an average quality score of 69.9% (SD ±15.7). Conclusions 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 PK/PD 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 additionally include the measurement of unbound concentrations for PK and target attainment evaluation.