Clinical application of vancomycin population pharmacokinetics model in patients with hematological diseases and neutropenia

Abstract

To explore the clinical application of a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases and neutropenia. Patients with hematological diseases and neutropenia were included in the PPK model study. Nonlinear mixed effect modeling approach (NONMEM) was used for model establishment. Monte Carlo simulation was carried out. A total of 74 patients were divided into model group and non-model group for clinical application research. The model group was given the initial dose of 1g q8h, and the non-model group was given 1g q12h as an empiric initial dosage. The follow-up dose adjustments were made according to the concentration results. This two-compartment model showed good stability and accuracy. The first trough concentration (C₀) and the compliance rate of the first C₀ were much higher in the model group than that in the non-model group (14.30 ± 4.73 μg/ml and 59.38% vs. 8.02 ± 2.61 μg/ml, 35.71%). Less patients needed dose adjustments and fewer adjustment times in the model group than those in the non-model group (12.50% and 0.13 ± 0.34 times vs. 50.00% and 0.61 ± 0.66 times). This suggested that for those patients who had a Creatinine clearance rate (CLCR) ≥ 90 ml/min/1.73 m², the initial dose of 1g q8h may help to reach the target C₀ (10∼20 μg/ml) quickly. It also helped to reduce the times and number of patients who need dose adjustments. Our PPK model of vancomycin in patients with hematologic diseases and neutropenia can be used to shorten the time to reach the target concentration and reduce the number of dose adjustments.Clinical trial registration: Not applicable (Retrospective study).