ABSTRACT
OBJECTIVE: To establish a population pharmacokinetics(PPK) model of teicoplanin(TEC) in Chinese adult patients and investigate the factors influencing TEC pharmacokinetic parameters. METHODS: A total of 222 blood samples and related information were prospectively collected from 139 inpatients with Gram-positive bacterial infection receiving TEC intravenously. A one-compartment model with first order elimination was used to perform the PPK analysis and the PPK model of TEC was developed via nonlinear mixed effects modeling(NONMEM) approach. The stability and prediction of the final model were evaluated by Bootstrap and normalized predictive distribution error (NPDE). Monte Carlo simulation was used to evaluate the effective of currently recommended dosing regimen. RESULTS: The creatinine clearance(CLcr) and albumin(ALB) were identified as the most significant covariate on the clearance rate of TEC. The established final model was: CL(L•h-1)=1.24×(CLcr/77)0.564×31/ALB;V(L)=69.2. It is verified that the established final model is stable, effective and predictable. For most patients with different serum albumin concentration and CLcr, the initial loading dose of 400 mg/q12h, iv, 3 times, and the maintenance dose of 400-800 mg•d-1 can achieve effective treatment of trough concentration. Severe infections need to adjust the loading dose to 800 mg/q12h, iv, 3 times, and maintain a dose of 400-800 mg•d-1 of the dosing regimens to ensure that the blood concentration reached 15 mg•L-1. CONCLUSION: This study reports that CLcr, ALB has a significant effect on TEC clearance and the model has important value for the individualization of TEC therapy in Chinese adult patients.