Population Pharmacokinetics of Tigecycline in Critically Ill Patients and Optimal Dosage Regimens With Dose Simulations Based on Infection Type and Renal Function

Background The present study was conducted to establish a population pharmacokinetic (PK) model that describes tigecycline concentrations in critically ill patients and optimises the detailed dosing regimens of tigecycline via Monte Carlo simulations. Methods A single‐centre, prospective, observational study was conducted on 155 patients hospitalised in the intensive care unit (ICU) with 458 plasma samples. This work enrolled 115 eligible patients (348 plasma samples) to establish the population PK model with various covariates and the other 40 patients (110 plasma samples) were validated on such a model. Monte Carlo simulations were performed to calculate the probability of target attainment (PTA) of proposal dosage regimens. Results The two‐compartment model of zero‐order absorption and first‐order elimination can be used to fully describe the concentration–time curve of tigecycline. The estimated values of population PK parameters were 16.3 and 40.7 L/h for clearance (CL) and Q , respectively, and 145 and 345 L for the volumes of the central and peripheral compartments. Creatinine clearance (CrCL) was the only factor that exhibited a relation to systemic CL in the final PK model, with a CrCL adjustment factor of 0.00692. According to dose simulations, the standard dosage regimen only sufficed for pneumonia patients with a low value of minimal inhibitory concentration (MIC = 0.25 mg/L) or renal dysfunction (MIC ≤ 1 mg/L, estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m 2 ). High doses of tigecycline were needed in such patients with a high MIC or a normal/high renal CL rate. For complicated intra‐abdominal infections, the standard dose can achieve a high PTA when MIC ≤ 0.5 mg/L and under nonaugmented renal CL conditions. For complicated skin‐structure infections, the standard dose can only achieve the expected therapeutic effect for patients with MIC = 0.25 mg/L and renal dysfunction (eGFR ≤ 60 mL/min/1.73 m 2 ). Conclusion The recommended standard dosage regimen of tigecycline is insufficient for most critically ill patients. This study provides detailed dose regimens of tigecycline for ICU patients based on infection type and renal function.