Abstract
AimsTo 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.MethodsPK 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.ResultsA 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.ConclusionsA 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.
Highlights
The pharmacokinetics (PK) and pharmacodynamics of many medications, including those used in the treatment of allergic diseases, have not been optimally investigated in paediatric populations [1]
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
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Summary
The pharmacokinetics (PK) and pharmacodynamics of many medications, including those used in the treatment of allergic diseases, have not been optimally investigated in paediatric populations [1]. For example, bad-tasting medicines and interruptions in their routines [2]. These difficulties should not stand in the way of research into appropriate medicines and/or formulations in this population, as children have the right to benefit from safe and efficacious treatments. The International Conference on Harmonisation (ICH) for Requirements for Registration of Pharmaceuticals for Human Use has issued guidelines [3] on the design of paediatric clinical trials to collect PK/pharmacodynamic, efficacy and safety data. Pain and anxiety related to the invasiveness of extraction and the volume of blood drawn as well as ethical considerations in the paediatric population are responsible for limited blood samples, and preclude the use of classical approaches to studies in children. Methods based on optimal design theory can lead to true optimisation of trial design [6] and have been used in the past for this purpose in other scenarios [7,8,9]
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