Population pharmacokinetic and pharmacodynamic model of norvancomycin

AIM: To evaluate the population pharmcokinetics (PPK) and pharmacodynamics(PD) of norvancomycin in patients. METHODS: We enrolled 146 patients who were confirmed or suspected with gram-positive bacterial infections in this study. A PPK model was developed and validated by the analysis of NONMEM software. The PK/PD profiles from the pharmacokinetic parameters in the patients and from MIC values were obtained. An optimal dose regime was calculated by the analyses of the PK/PD model according to the clinical outcomes and bacterial tests. The norvancomycin MICs of clinically isolated strains from the patients population were determined by agar dilution methods. RESULTS: The best model was a two compartment pharmacokinetic model with exponential interindividual error and additive residual error statistical models. The finding of the study indicated that the change in Ccr values had impacts on drug clearance (CL). For example, CL of patients with decreased renal function would be influenced. The increased volume of a peripheral distribution (V2) was observed when norvancomycin was co-administered with diuretics. The logistic stepwise analyses revealed that ratio of AUC24/MIC is a major factor which could significantly determine the clinical outcomes and bacterial eradication for patients. When the ratio of AUC24/MIC was more than 579.90 for Staphylococcus aureus infections or it was more than 637.67 for Enterococcal infections, approximately 95% of patients could achieve cure clinical outcome. CONCLUSION: AUC0-24/MIC should be a major PK/PD parameter to determine efficacy of norvancomycin. An optimized regimen of norvancomycin can be simulated and developed for different subgroups of bacterial infected patients with special physiologic and pathologic features.