Population pharmacokinetic modelling of rupatadine solution in 6-11 year olds and optimisation of the experimental design in younger children.

Abstract

AIMS:To optimise a pharmacokinetic (PK) study design of rupatadine for 2-5 year olds by using a population PK model developed with data from a study in 6-11 year olds. The design optimisation was driven by the need to avoid children's discomfort in the study. METHODS:PK data from 6-11 year olds with allergic rhinitis available from a previous study were used to construct a population PK model which we used in simulations to assess the dose to administer in a study in 2-5 year olds. In addition, an optimal design approach was used to determine the most appropriate number of sampling groups, sampling days, total samples and sampling times. RESULTS:A two-compartmental model with first-order absorption and elimination, with clearance dependent on weight adequately described the PK of rupatadine for 6-11 year olds. The dose selected for a trial in 2-5 year olds was 2.5 mg, as it provided a Cmax below the 3 ng/ml threshold. The optimal study design consisted of four groups of children (10 children each), a maximum sampling window of 2 hours in two clinic visits for drawing three samples on day 14 and one on day 28 coinciding with the final examination of the study. CONCLUSIONS:A PK study design was optimised in order to prioritise avoidance of discomfort for enrolled 2-5 year olds by taking only four blood samples from each child and minimising the length of hospital stays.