Pharmacokinetics, safety and population pharmacokinetics/pharmacodynamics analysis of meropenem-vaborbactam in Chinese healthy participants.

Background: Meropenem-vaborbactam is a fixed-dose β-lactam/β-lactamase inhibitor combination active against carbapenem-resistant Methods: This single-center, open-label study included 20 healthy participants divided into two groups receiving meropenem-vaborbactam (1:1) at 1 g/1 g or 2 g/2 g via 3-h infusion. Plasma and urine concentrations of meropenem, its open-ring metabolite, and vaborbactam were analyzed using a validated liquid chromatography-tandem mass spectrometry method. PK analysis was conducted using WinNonlin. Monte Carlo simulations were used to evaluate the 1 g/1 g and 2 g/2 g regimens administered every 8 h as 3-h intravenous infusions. For the standard 2 g/2 g regimen, the impact of extending the infusion duration from 3 to 4 h was further evaluated based on the FDA-recommended PK/PD target. Results: Plasma concentrations of meropenem, its open-ring metabolite, and vaborbactam peaked immediately after infusion, with rapid distribution and elimination. Exposure increased proportionally with dose, and almost no accumulation was observed after repeated 8-hourly dosing. Most meropenem (68.5%-77.0%) and nearly all vaborbactam were excreted unchanged in urine. Both single and multiple doses were well tolerated, with no severe or serious adverse events. In addition, PK/PD analysis showed that, for CRE isolates, the standard 2 g/2 g every 8 h regimen with a 3-h intravenous infusion achieved ≥90% probability of target attainment for meropenem (45% Conclusion: The standard meropenem-vaborbactam regimen (2 g/2 g every 8 h, 3-h intravenous infusion) demonstrated favorable PK and safety profiles, with PK/PD analyses supporting the appropriateness of the standard regimen in Chinese participants, consistent with global findings. These results provide PK/PD support for the standard regimen and warrant further evaluation in Chinese patients with CRE infections.