Population pharmacokinetic model of oral minocycline in critically ill adult patients with ventilator-associated pneumonia.

Objectives: Multidrug-resistant Acinetobacter baumannii (MDR-A. baumannii) has become an emerging pathogen, causing ventilator-associated pneumonia (VAP), with limited treatment options available. MIN has re-emerged as a potential treatment option for MDR pathogens. However, evidence regarding MIN pharmacokinetic properties in critically ill patients is scarce and primarily limited to IV administration. To address the knowledge gap in regions where IV MIN is unavailable, a prospective, open-label study was conducted to describe the pharmacokinetic properties of orally administered MIN.

Methods: The study included 24 critically ill patients with MDR-A. baumannii VAP. A population PK (popPK) model was developed and the PTA for different MICs was assessed by Monte Carlo simulations. A one-compartment model with first-order absorption and linear elimination best described the data.

Results: The values of the estimated population parameters were found equal to 183.3 L, 6.55 L/h and 1.66 h⁻¹, for the apparent volume of distribution (V/F), the apparent clearance (CL/F) and the absorption rate constant (ka), respectively (F representing oral bioavailability). PTA analysis showed that for a daily dose of 400 mg, adequate exposure [free AUC/MIC (fAUC/MIC > 25)] was achieved only for MICs ≤ 0.25 mg/L, while for the ratio of fAUC/MIC = 13.75, high PTA values are calculated up to MIC = 0.5 mg/L.

Conclusions: This study provides a popPK model for oral MIN in critically ill adults. The developed popPK model contributes to a better understanding of MIN's PK and can inform dosing strategies and future studies on MIN use in critical care settings.