Methods: All data analyses were performed using NONMEM®. A population pharmacokinetic model was first developed from vancomycin dosage and concentration data collected during routine therapeutic drug monitoring in 398 patients, then new vancomycin dosage guidelines were devised by using the model to predict vancomycin trough concentrations in a simulated dataset. Individual estimates of CL and V1 were then obtained in an independent group of 100 patients using the population model and the POSTHOC option. These individual estimates were used to predict vancomycin trough concentrations and steady-state AUC24/MIC ratios using the current and new dosage guidelines.
Results: The population analysis found that the vancomycin data were best described using a bi-exponential elimination model with a typical CL of 3.0 L/h that changed by 15.4% for every 10 mL/min difference from a CLCR of 66 mL/min. Vss was 1.4 L/kg. The proposed dosage guidelines were predicted to achieve 55% of vancomycin troughs within 10-15 mg/L and 71% within 10-20 mg/L, which is significantly higher than current guidelines (19% and 22%, respectively). The proportion of AUC24/MIC ratios above 400 was also higher, 87% compared with 58%.
Conclusions: New vancomycin dosage guidelines have been developed that achieve trough concentrations of 10-15 mg/L earlier and more consistently than current guidelines.
- population pharmacokinetics
- therapeutic drug monitoring
- antimicrobial agents
Alison Thomson (Participant)
Impact: Impact - for External Portal › Professional practice, training and standards, Health and welfare - new products, guidelines and servicesFile