AUTHOR=Su Wei , Song Shuping , Liu Jieqiong , Yu Haitao , Feng Binbin , Wu Yinshan , Guo Feng , Yu Zhenwei 

TITLE=Population pharmacokinetics and individualized dosing of tigecycline for critically ill patients: a prospective study with intensive sampling

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1342947

DOI=10.3389/fphar.2024.1342947

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Due to the heterogeneity of critically ill patients, the pharmacokinetics of tigecycline are unclear, and the optimal dosing strategy is controversial.</p><p><bold>Methods:</bold> A single-center prospective clinical study that included critically ill patients who received tigecycline was performed. Blood samples were intensively sampled (eight samples each), and plasma drug concentrations were determined. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis and visual predictive checks. Monte Carlo simulation was conducted to optimize the dosage regimen.</p><p><bold>Results:</bold> Overall, 751 observations from 98 patients were included. The final PPK model was a two-compartment model incorporating covariates of creatinine clearance on clearance (CL), body weight on both central and peripheral volumes of distribution (V1 and V2), γ-glutamyl transferase and total bilirubin on intercompartment clearance (Q), and albumin on V2. The typical values of CL, Q, V1 and V2 were 3.09 L/h, 39.7 L/h, 32.1 L and 113 L, respectively. A dosage regimen of 50 mg/12 h was suitable for complicated intra-abdominal infections, but 100 mg/12 h was needed for community-acquired pneumonia, skin and skin structure infections and infections caused by less-susceptive bacteria.</p><p><bold>Conclusion:</bold> The Tigecycline PPK model was successfully developed and validated. Individualized dosing of tigecycline could be beneficial for critically ill patients.</p>