![nonmem weighted optimization nonmem weighted optimization](https://www.researchgate.net/publication/332805351/figure/tbl1/AS:754126073917440@1556809075079/Control-Stream-Code-Segments-Showing-Relevant-Code.png)
More extensive inter- and intra-individual variability in pharmacokinetics has been described for neonates, compared to adults, and a larger variability in drug disposition and a poor relation between the dose administered and the concentration achieved in neonates has been recorded for most drugs 5, 6. Neonates exhibit major and rapid physiological changes in drug distribution, metabolism, excretion, and absorption (for drugs after parenteral administration) 4. Neonates with suspected sepsis typically receive vancomycin. aureus cases in intensive care units and has become a threat to critically ill populations in Korea 3.
![nonmem weighted optimization nonmem weighted optimization](https://i1.rgstatic.net/publication/51815963_Comparison_of_Nonmem_72_estimation_methods_and_parallel_processing_efficiency_on_a_target-mediated_drug_disposition_model/links/559a8c8f08ae5d8f3937dab6/largepreview.png)
aureus (MRSA) accounts for 80% of all isolated S. According to the Korean Neonatal Network, the overall incidence of sepsis among low-birth weight infants was 21%, with gram-positive organisms being the most prevalent organisms: coagulase-negative Staphylococcus is most common, followed by Staphylococcus aureus 2. Neonates, especially premature infants, are susceptible to gram-positive infections 1. A higher dosage regimen than the typical recommendation is suggested. Population pharmacokinetic modeling and dose optimization of vancomycin in Korean neonates showed that vancomycin clearance was related to PMA and CLcr, as well as body weight. Postmenstrual age (PMA) and creatinine clearance (CLcr) affected the clearance of vancomycin, and model evaluation confirmed the robustness of the final model. A one-compartment model with first-order elimination best described the vancomycin pharmacokinetics in neonates. Only 37.4% of the analyzed concentrations were within trough concentrations 5–15 µg/mL. The patient cohort included 207 neonates, and 900 vancomycin concentrations were analyzed. The predictive performance of the final model was developed, and dosing strategies were explored using Monte Carlo simulations with AUC 0–24 targets 400–600. Allometric and isometric scaling was applied to standardize pharmacokinetic parameters for clearance and volume of distribution, respectively, using fixed powers (0.75 and 1, respectively, for clearance and volume). One- and two-compartment models with first-order elimination were evaluated as potential structural pharmacokinetic models. We applied nonlinear mixed-effect modeling to build the population pharmacokinetic model. Vancomycin concentrations were collected based on therapeutic drug monitoring, and other patient characteristics were gathered through electronic medical records. From a retrospective chart review, neonates treated with vancomycin from 2008 to 2017 in a neonatal intensive care unit (NICU) were included. The pharmacokinetics of vancomycin vary among neonates, and we aimed to conduct population pharmacokinetic analysis to determine the optimal dosage of vancomycin in Korean neonates.