Objectives: The objective was to evaluate the pharmacokinetic and pharmacodynamic properties of a single intravenous fixed dose compared with a weight-adjusted dose of linezolid.
Methods: A Phase I, comparative clinical trial was conducted involving 20 healthy male Chinese volunteers, assigned into low weight (LW) (50 kg < weight ≤ 55 kg) and high weight (HW) (≥ 80 kg) groups. All subjects were administrated single dose of linezolid (600 mg/30 min) and, after 72 h washout period, another single-dose (10 mg/kg/30 min). Plasma linezolid concentrations were measured by liquid chromatography-tandem mass spectrometry. A Monte Carlo simulation was used to evaluate the probability of pharmacodynamic target attainment (PTA).
Results: With 600 mg dose, plasma concentrations in LW group were much higher than that in HW group. A persistent serum inhibitory activity was observed in LW group; the inhibitory activity was lower in HW group. The PTA in HW group was lower than in LW group. For 10 mg/kg dose, both HW and LW groups had similar plasma concentrations. The HW and LW groups had similar serum inhibitory effects. The PTA in HW and LW groups also showed no difference.
Conclusions: Our findings suggest that a weight-adjusted, 10 mg/kg regimen of linezolid may be more appropriate than fixed dosing for patients of different body weight.