Year: 2025
Type: article
Abstract: BACKGROUND: The fixed-dose combination of aztreonam/avibactam is administered with a loading dose (LD), resulting in systematic drug wastage in patients with preserved renal function. Whether the LD can be reduced remains unclear. OBJECTIVES: To evaluate in silico the pharmacokinetic (PK) and pharmacodynamic (PD) consequences of reducing the current LD in patients with normal renal function, using a population PK model and Monte Carlo simulations. METHODS: A published two-compartment population PK model was implemented. We performed 10 000 Monte Carlo simulations of virtual patients with normal renal function (creatinine clearance > 80 mL/min), receiving the standard LD (2 g/0.67 g over 3 h) or a reduced LD (1.5 g/0.5 g over 3 h), followed by standard maintenance doses every 6 h. PK metrics (C0, AUC) and probability of target attainment were compared between the two regimens. RESULTS: Reducing the LD decreased early exposure (AUC0-24 h) from 1281 ± 497 to 1200 ± 464 mg h/L for aztreonam and from 276 ± 118 to 258 ± 110 mg h/L for avibactam, but steady-state AUC24-48 h was identical between regimens. PTA differences for intermediate PD thresholds were modest and transient. CONCLUSIONS: Lowering the LD in patients with preserved renal function had only a short-lived impact on early exposure and did not compromise PK/PD performance. These results support dose adaptation to reduce unnecessary drug waste.
DOI: 10.1093/jac/dkaf421
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4416987190