Iftekhar Mahmood*
Mahmood et al. J Clin Transl Res 2022; 8(5):3
Published online: September 7, 2022
Abstract
Background and aim: In order to conduct a pediatric clinical trial, it is important to optimize pediatric dose as accurately as possible. This is mainly because due to ethical reasons, children cannot be given several doses to evaluate pharmacokinetics, safety, and efficacy of a drug.
Methods: In this study, several simple methods to project a first-in-pediatric dose to initiate a clinical trial were evaluated. These methods were: 1. Weight-based pediatric dose prediction (allometric scaling), 2. Salisbury Rule (weight-based method), and 3. Pediatric dose prediction based on predicted clearance. These methods were compared with the dose given to children in clinical practice. The methods were also compared with whole body PBPK model (n =11). A ±30% prediction error (predicted vs observed) was considered acceptable.
Results: There were 27 drugs with 113 observations (different age groups from preterm neonates to adolescents). At least, ≤30% prediction error in pediatric dose projection was noted for more than 70% observations. The predictive performance of all the proposed methods were comparable with the whole body PBPK.
Conclusion: The proposed methods are simple and accurate and can be developed on a spreadsheet in a very short period of time.
Relevance for patients: The study provides an estimate of first-in-pediatric dose by simple methods to initiate pediatric clinical trials. Especially, Salisbury Rule which is based on body weight and is very simple and works fairly well in children >30 kg body weight and can be even used in clinical settings.
DOI: http://dx.doi.org/10.18053/jctres.08.202205.003
Author affilation
Mahmood clinical pharmacology consultancy, LLC. 1709, Piccard DR, Rockville, MD 20850, USA
*Corresponding author
Iftekhar Mahmood
Mahmood clinical pharmacology consultancy, LLC. 1709, Piccard DR, Rockville, MD 20850, USA
Tel: +1 301-838-4555
Email: Iftekharmahmood@aol.com
Handling editor:
Michal Heger
Department of Pharmaceutics, Utrecht University, the Netherlands
Department of Pharmaceutics, Jiaxing University Medical College, Zhejiang, China
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