Pharmacokinetics and Pharmacodynamics of Linezolid following Intragastric and Intravenous Administrations in ICU Patients

Abstract Background. Though intravenous infusion linezolid therapy is common for patients in the intensive care unit (ICU), intragastric linezolid therapy is also provided for those whose gastrointestinal function are feasible. If intragastric linezolid acquired similar pharmacokinetics (PK) and pharmacodynamics (PD) parameters, this might be preferred based on cost and ease of liquid volume management.Methods. Patients in the ICU treated with intragastric and intravenous linezolid were included. Serial blood samples were collected and linezolid concentrations were measured. PK data were analyzed using Pmetrics. Monte Carlo simulations were used to evaluate PD target achievement. Results. Tmax was 1.06 ± 0.82 h of the study period in 10 patients receiving intragastric linezolid and 0.65 ± 0.24 h in 10 patients receiving intravenous linezolid (p<0.001). Cmax was 9.07 ± 4.99 mg/mL of patients with intragastric linezolid and 12.30 ± 4.06 mg/mL of patients with intravenous linezolid (p=0.904). Clearance was 11.99 ± 11.24 L/h in patients with intragastric linezolid and 14.48 ± 3.56 L/h in patients with intravenous linezolid (p=0.342). For infections with a microorganism with a minimum inhibitory concentration (MIC) of 2 mg/L, simulations demonstrated that with 600 mg every 12 hours, 58.22% would have a linezolid concentration greater than the MIC during 100% of the dosing interval (%T > MIC = 100%) in intragastric group, whereas this was 71.36% in intravenous group. Higher SOFA score and body weight were associated with lower probability of target attainment (PTA) of linezolid with standard regimen.Conclusions. Patients in ICU may be at high risk for underexposure to linezolid by intragastric administration, especially when their SOFA score and body weight is high and when infected with pathogens with an MIC ≥ 2 mg/L.