Contezolid for the Super-Elderly: Balancing Efficacy and Safety Through Pharmacokinetic Insights.

Background: Contezolid is a new oxazolidinone antibacterial agent, and its pharmacokinetic (PK) characteristics and safety in super-elderly patients remain poorly understood. Methods: Contezolid PK parameters were analyzed in enrolled super-elderly patients (≥ 80 years), with systematic assessment of steady-state profiles and adverse events. Results: Thirteen super-elderly patients (mean age: 94.9 ± 4.8 years) were included in the study. The plasma concentrations of contezolid peaked at 2-3h post administration. Both Cmax and AUC0-t exhibited dose-dependent increases across regimens (400 mg q24h, 400 mg q12h, and 800 mg q12h). When receiving a dosage of 800 mg q12h, super-elderly patients demonstrated comparable Cmax (20.32 vs 26.45 mg/L), AUC0-t (97.80 vs 90.38 h·mg/L), and clearance (9.08 vs 10.20 L/h) values to those of healthy adults but prolonged Tmax (2.67 vs 0.57 h) and shorter t1/2 values (2.33 vs 4.84 h). For pathogens with a minimum inhibitory concentration (MIC) ≤1 mg/L, 400 mg of contezolid q12h resulted in a > 90% probability of target attainment (PTA), whereas doubling the dose to 800 mg q12h resulted in a PTA > 90% against pathogens with MICs of 2-4 mg/L. Contezolid was well tolerated, with mild gastrointestinal adverse reactions (vomiting, n=2) and elevated AST (n=1), γ-GT (n=2), and lipase (n=1) levels. According to a self-controlled analysis of 9 patients who switched from linezolid to contezolid, the incidence of thrombocytopenia was significantly lower when taking contezolid (11.1% vs 77.8%). Conclusion: Contezolid has comparable PKs in super-elderly and healthy adults. While a dosage of 400 mg q12h is sufficient for pathogens with MICs ≤ 1 mg/L, a higher dosage of 800 mg q12h is recommended for higher MICs (2-4 mg/L), with both doses demonstrating favorable safety. Clinical Trial Registration Number: ChiCTR2200056377; 4/2/2022.