Weight-adjusted versus fixed dose of linezolid for Chinese healthy volunteers of higher and lower body weight: a Phase I pharmacokinetic and pharmacodynamic study

Abstract

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.