Population Pharmacokinetics Study Of Vancomycin, And Compare The Dosage Regimen Of Vancomycin And Linezolid For Treatment Of Gram-positive Cocci Infections

Objective: To develop a population pharmacokinetic model of intravenous vancomycin. To estimate and optimize the dosage regimen of vancomycin and linezolid for different Gram-positive cocci infections. Methods: The concentration-time data of 276 volunteers in ten literatures collected from Wanfang,VIP,CNKI and PubMed database were used to build the PPK model of vancomycin by using NONMEM. The influence of infection and demographic factors on PPK parameters was estimated, and the final PPK model was validated by Bootstrap method. To collect the pharmacokinetic data of vancomycin and linezolid, and the pharmacodynamics in vitro of these drugs for staphylococcus epidermidis, staphylococcus aureus, enterococcus faecalis and enterococcus faecium. Then simulate different dosage regimens of two drugs against four types of bacteria by MCS model, and compare the CFRs of all regimens. Results: A one-compartment model was adopted as a PPK model. The typical population values of vancomycin clearance and apparent volume of distribution were 3.35L/h and 42.8L respectively. The estimated clearance for patients with infection was lower than healthy volunteers but the apparent volume of distribution were higher. Final model has been validated by Bootstrap method, showing good stability and predictive efficacy. When MIC = 0.25、0.5 mg/L, The regimen of vancomycin 1500mg/d or linezolid 400 mg q12h are recommended; when MIC = 1 mg/L, the recommended dose of vancomycin increases to 2000mg/d while dose of linezolid is still 400 mg q12h; when MIC = 2 mg/L, the recommended dose of vancomycin increases to 3500mg/d while dose of linezolid is still 400 mg q12h; when MIC ≥ 4mg/L, there is no dosing regimen of vancomycin or linezolid achieve a satisfactory antibacterial activity, so they were recommended combination therapy. Conclusion: The population pharmacokinetic model of intravenous vancomycin in healthy people were one-compartment models with first-order absorption and elimination and first-order elimination.The infection may influence the CL and Vd values of vancomycin. The typical population values, such as CL and V were 3.35 L/h and 42.8L The regimen of vancomycin 3500 mg/d against staphylococcus epidermidis was recommended. The regimen of vancomycin 3000 mg/d against staphylococcus aureus was recommended. The regimens of vancomycin 3000 mg/d or linezolid 400 mg q12 h against enterococcus faecalis were recommended. The regimens of vancomycin 2000 mg/d or linezolid 400 mg q12 h against enterococcus faecium were recommended.