Relationship between body weight and postmenstrual age in a Korean pediatric population

Abstract

Weight is a covariate representative of body size and is known to influence drug disposition. Recently, with increased use of allometric scaling, this variable has become more significant in accounting for variability in pharmacokinetic parameters. In adults, weight can be considered as a time invariant covariate because physical development is complete. As a result, when weight is missing in data, the typical or median value (say, 70 kg) could be imputed. On the contrary, weight continuously changes with age in the pediatric population. In this case, it is more appropriate to consider different median weight for each age group. We constructed a prediction model for weight using postmenstrual age (PMA) with the data consisting of 83,014 Korean pediatric patients. Weight, PMA, and gender information were collected from electronic medical records. Sigmoid models multiplied by exponential or logistic function were tested for basic model structure. Covariate effects on model parameters were then investigated using selection criteria of p < 0.001. All analyses were performed using NONMEM 7.3.0 and R3.2.0. The sigmoid model multiplied by logistic function best described the data and there was a significant difference between boys and girls in model parameters. It is expected that the results obtained in this work can be used for imputation of missing weights in pediatrics when PMA is available. In addition, the developed model can be used for clinical studies in children under 12 years old whose weight change rapidly with age and for model building in dealing with time varying body weight as a covariate.

Population Pharmacokinetics and Dosing Optimization of Linezolid in Pediatric Patients

“…After the covariate screening procedure, only WT and eGFR elucidated significant portions of the variance and were included into the final PopPK model. As a covariate representing body size, WT is generally known to have a significant impact on drug disposition (18,19), especially for pediatric patients. So far, the clearance pathways of linezolid have not been fully illustrated.…”