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

Mandy Wan, Bruce Green, Arpana Iyengar, Nivedita Kamath, Hamsa Reddy, Jyoti Sharma, Jyoti Singhal, Susan Uthup, Sudha Ekambaram, Sumithra Selvam, Greta Rait, Rukshana Shroff, Jignesh Patel

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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Abstract

AIMS: 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 weight-based dosing strategy.

CONCLUSION: This is the first study to describe the population PK of colecalciferol in children with CKD. PK model informed dosing is expected to improve the attainment of target 25(OH)D concentrations, while minimising the risk of overdosing.

Original languageEnglish
Article numberdoi.org/10.1111/bcp.15064
Pages (from-to)1223-1234
Number of pages12
JournalBritish Journal of Clinical Pharmacology
Volume88
Issue number3
Early online date30 Sept 2021
DOIs
Publication statusPublished - Mar 2022

Keywords

  • Child
  • Female
  • Humans
  • Male
  • Renal Insufficiency, Chronic/complications
  • Vitamin D Deficiency/drug therapy

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