Sampling Optimisation in Pharmacokinetic Bridging Studies: Example on the Use of Deferiprone in Children With Β-Thalassaemia
Abstract
Despite the wide clinical experience with deferiprone, the optimum dosage in children aged less than 6 years remains to be established. This analysis is aimed at optimising the design of a prospective clinical study for the evaluation of deferiprone pharmacokinetics in children. A one-compartment model with first order oral absorption was used for the purposes of the analysis. Different sampling schemes were evaluated under the assumption of a constrained population size. A sampling scheme with 5 samples per subject was found to be sufficient to ensure accurate characterisation of the pharmacokinetics of deferiprone. Whereas the accuracy of parameters estimates was high, precision was slightly reduced due to the small sample size (> 30% for Vd/F and KA). AUC values (mean and SD) were found to be 33.37 (19.24) and 35.61 (20.22) mg/L.h and Cmax values 10.17 (6.05) and 10.94 (6.68) mg/L in sparse and frequent sampling, respectively. The results show that predefined sampling schemes and sample sizes do not warrant accurate model and parameter identifiability. ED-optimality and simulation-based optimisation concepts can be used to support PK bridging studies. Of importance is the accurate estimation of the magnitude of the covariate...Continue Reading
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