Bioequivalence of four oral prednisolone formulations in children with
asthma or asthma-like exacerbations
Abstract
Introduction This study aimed to describe the levels of exposure to
different forms of prednisolone in children with asthma or asthma-like
symptoms, ages six months to seventeen years old, treated with crushed
tablets, oro-dispersible tablets, a liquid suspension, or whole tablets.
Methods Participants were randomized to received two out of four
different formulations on successive days using a single-center,
open-label, two-period, cross-over design. Saliva samples were collected
to measure prednisolone concentrations, and a population pharmacokinetic
model was used to analyze the data. The bioequivalence of the test drug
to the whole tablet was determined using the 90% confidence interval of
the ratios of area under the curve (AUC) and maximum concentration
(Cmax). Results This study enrolled 41 children, with a mean age of 4.9
years ± 3.7 and a mean weight of 21.8 kg ± 10.9; 61% were boys. The
pharmacokinetic data were best described by a two-compartment model
using plasma concentrations calculated from saliva. The population mean
clearance was 317±156 ml/min/70kg, with a mean half-life of 5.3 ± 3.2
hours and a volume of distribution of 141 L/70kg. The liquid suspension
demonstrated bioequivalence to the control (whole tablets) in terms of
AUC. However, none of the tested formulations were bioequivalent
regarding to Cmax. Conclusion The tested formulations did not exhibit
bioequivalence (AUC and Cmax) when compared to the whole tablet. Using
different prednisolone formulations interchangeably may be challenging,
especially in a pediatric population where inter-individual and residual
variability in the pharmacokinetics seemed to have significant impact on
exposure.