Two simple methods to predict Pediatric Dose of Antituberculosis Medicines: Application of Allometry and Salisbury Rule

Background: In drug development, selecting the first-in-human dose is crucial. Similarly, in pediatric drug development, determining the first-in-pediatric dose is of paramount importance. Given that the pharmacokinetic, safety, and efficacy of a product are generally well established in adults, this information can be used to select an appropriate first-in-pediatric dose for pediatric clinical trials. Methods: Two simple methods – Salisbury Rule and allometric scaling – were evaluated for predicting the first-in-pediatric dose to initiate a clinical trial for antituberculosis medicines. To assess the predictive performance of these methods, the predicted doses were compared with the observed doses recommended by the World Health Organization (WHO) or the United States Food and Drug Administration (US FDA). Results: This study included seven antituberculosis drugs with 62 observations across different body weight groups. The predictive accuracy of both methods was excellent, with over 80% of the observations falling within a 30% prediction error. Conclusion: The predicted pediatric doses of antituberculosis drugs using the two proposed methods reconciled well with the recommended human doses from WHO or the US FDA. The methods are simple and can easily be calculated on a spreadsheet or calculator in a short amount of time. Relevance for patients: These two approaches are helpful for optimizing the selection of appropriate antituberculosis medication dosages in pediatric patients with tuberculosis, ensuring effective treatment, and minimizing potential risks.