Application of Allometric Scaling and Salisbury Rule for the Prediction of Antimalarial Drugs for First-in-Pediatric Dose Selection.

Abstract

Background: In pediatric drug development, the selection of first-in-pediatric dose is of immense importance. Generally, the pharmacokinetic information and a safe and efficacious dose of a drug in adults are already known and this information can then be used to select first-in-pediatric dose. The objective of this study was to predict the pediatric dose of antimalarial drugs and compare the predicted dose with the recommended dose.

Methods: In this study, two simple methods to project a first-in-pediatric dose to initiate a clinical trial for antimalarial drugs were evaluated. These two methods were Salisbury Rule and allometric scaling. The predicted doses of antimalarial drugs by the two methods were compared with the observed doses recommended by the World Health Organization (WHO) or the US Food and Drug Administration (FDA).

Results: In this study, 15 antimalarial drugs with 88 observations (different body weight groups) were evaluated. From allometric scaling, all 88 observations were within 0.5-1.5-fold and 0.7-1.3-fold prediction error. From Salisbury Rule, all 88 observations were within 0.5-1.5-fold and 86 observations were within 0.7-1.3-fold prediction error.

Conclusions: The proposed methods are simple and quite accurate in their predictive power. These methods can be developed on a spreadsheet or a calculator in a very short period of time and are applicable to first-in-pediatric clinical trials or even in a clinical setting.