Building vancomycin population pharmacokinetic model for Japanese low birth weight infants in comparing it with previously reported pediatric population pharmacokinetic models.

Abstract

Background and objectives: Vancomycin (VAN) is one of therapeutic agents for severe infections, and its efficacy and safety are subject to therapeutic drug monitoring. However, there is a lack of data regarding the administration of VAN to low birth weight (LBW) infants. This presents a challenge to ensure optimal dosing and maximize the benefits of VAN therapy in this specialized patients.

Materials and methods: VAN serum samples were collected through opportunistic sampling for clinical use. Population Pharmacokinetics (PopPK) analysis was conducted with a one-compartment model in a nonlinear mixed-effects model using Phoenix NLME (Certara ver.8.4). We compared the final model with the 12 previously reported PopPK models.

Results: A total of 106 samples from 25 patients were obtained to establish the PopPK model for LBW infants. We successfully developed one-compartment PopPK model using Phoenix NLME based on Japanese LBW infants receiving VAN with body weights of less than 2,500 g. The covariates in our PopPK model are postmenstrual age, body weight, and serum creatinine for clearance and postnatal age for volume of distribution. A comparison of the goodness-of-fit metrics indicated that our PopPK model achieved better prediction accuracy for VAN blood concentrations, as indicated by the lower values of these metrics.

Conclusion: We successfully established a PopPK model incorporating PNA and PMA as new covariates. By addressing the issue of data scarcity in LBW infants, our study provides insights and strategies to manage VAN therapy in LBW infants, thus optimizing its effectiveness and safety.