Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease

Abstract

The prevalence of vitamin D deficiency is high in children with chronic kidney disease (CKD). However, current dosing recommendations are based on limited pharmacokinetic (PK) data. This study aimed to develop a population PK model of colecalciferol that can be used to optimise colecalciferol dosing in this population.Methods: Data from 83 children with CKD were used to develop a population PK model using a nonlinear mixed effects modelling approach. Serum creatinine and type of kidney disease (glomerular vs. nonglomerular disease) were investigated as covariates, and optimal dosing was determined based on achieving and maintaining 25-hydroxyvitamin D (25(OH)D) concentration of 30-48 ng/mL. Results:The time course of 25(OH)D concentrations was best described by a 1-compartment model with the addition of a basal concentration parameter to reflect endogenous 25(OH)D production from diet and sun exposure. Colecalciferol showed wide between-subject variability in its PK, with total body weight scaled allometrically the only covariate included in the model. Model-based simulations showed that current dosing recommendations for colecalciferol can be optimised using a weightbased dosing strategy.

Hypervitaminosis D and nephrocalcinosis: too much of a good thing?

“…It may also point to a need to consider a more optimized dosing strategy in younger children. Lin et al did not explore the association between 25(OH)D concentrations and dose [30], but other studies have suggested the need for body size-based dosing for vitamin D [38][39][40]. In CKD patients, our population pharmacokinetic model lends support for weight-based dosing, with model-based simulation showing improvement in attainment of target 25(OH)D concentrations while minimizing the risk of overdosing [40].…”

Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce

“…Likewise, the change in 25(OH)D levels was positively associated with vitamin D dosage [ 97 ]. Model-based simulations showed that current dosing recommendations for cholecalciferol can be optimized using a weight-based dosing strategy [ 98 ].…”