Wan, M;
Green, B;
Iyengar, AA;
Kamath, N;
Reddy, HV;
Sharma, J;
Singhal, J;
... Patel, JP; + view all
(2021)
Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease.
British Journal of Clinical Pharmacology
10.1111/bcp.15064.
(In press).
Preview |
Text
bcp.15064.pdf - Published Version Download (3MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/bcp.15064 |
| Publisher version: | https://doi.org/10.1111/bcp.15064 |
| Language: | English |
| Additional information: | © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | chronic kidney disease, colecalciferol, population pharmacokinetics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10135750 |
Archive Staff Only
 |
View Item |
