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.
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References
Talapharmacokineticso J, Skrlec I, Alebi T, Juki M, Vcev A. Malaria: the past and the present. Microorganisms. 2019;7:179.
Mahmood I. Dosing in children: a critical review of the pharmacokinetic allometric scaling and modelling approaches in paediatric drug development and clinical settings. Clin Pharmacokinet. 2014;53:327–46.
Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology: drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349:1157–67.
Green DJ, Zineh I, Burckart GJ. Pediatric drug development: outlook for science-based innovation. Clin Pharmacol Ther. 2018;103:376–8.
Abernethy DR, Burckart GJ. Pediatric dose selection. Clin Pharmacol Ther. 2010;87:270–1.
Elias GP, Antoniali C, Mariano RC. Comparative study of rules employed for calculation of pediatric drug dosage. J Appl Oral Sci. 2005;13:114–9.
Mahmood I. Dose selection in children. In: Pharmacokinetic allometric scaling in pediatric drug development. Rockville: Pine House Publishers; 2013. p. 151–60.
Lack JA, Stuart-Taylor ME. Calculation of drug dosage and body surface area of children. Br J Anaesth. 1997;78:601–5.
Munzenberger PJ, McKercher P. Pediatric dosing-the pharmacist’s dilemma. Contemp Pharm Pract. 1980;3:11–4.
Mahmood I. A comparison of different methods for the first-in-pediatric dose selection. J Clin Transl Res. 2022;8:369–81.
Mahmood I. A simple method for the prediction of therapeutic proteins (monoclonal and polyclonal antibodies and non-antibody proteins) for first-in-pediatric dose selection: application of salisbury rule. Antibodies. 2022;11(66):2–12.
WHO. Guidelines for the treatment of malaria. 3rd ed. World Health Organization; 2015.
FDA package insert of FANSIDAR (sulfadoxine and pyrimethamine), 1996.
FDA package insert of COARTEM (artemether/lumefantrine), 2009.
FDA package insert of MALARONE(atovaquone and proguanil hydrochloride), 2008.
FDA package insert of LARIAM (mefloquine hydrochloride), 2003.
FDA package insert of PLAQUENIL (HYDROXYCHLOROQUINE SULFATE), 2015.
FDA package insert of CHLOROQUINE PHOSPHATE, 2009.
Mahmood I. Dose selection in children: allometry and other methods. In: Pediatric pharmacology and pharmacokinetics. Rockville: Pine House Publishers; 2008. p. 184–216.
Mansoor N, Ahmad T, Alam Khan R, Sharib SM, Mahmood I. Prediction of clearance and dose of midazolam in preterm and term neonates: a comparative study between allometric scaling and physiologically based pharmacokinetic modeling. Am J Ther. 2019;26:e32–7.
Senarathna SM, Batty KT. Interspecies allometric scaling of antimalarial drugs and potential application to pediatric dosing. Antimicrob Agents Chemother. 2014;58:6068–78.
Mahmood I, Cheng A, Brauer E, Humeniuk R. Prediction of antimalarial drug clearance in children: a comparison of three different interspecies scaling methods. Eur J Drug Metab Pharmacokinet. 2016;41:767–75.
Deyme L, Benzekry S, Ciccolini J. Mechanistic models for hematological toxicities: Small is beautiful. CPT Pharmacomet Syst Pharmacol. 2021;10:396–8.
Box GEP. Science and statistics. J Am Stat Assoc. 1976;71:791–9.
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Mahmood, I. Application of Allometric Scaling and Salisbury Rule for the Prediction of Antimalarial Drugs for First-in-Pediatric Dose Selection. Eur J Drug Metab Pharmacokinet 48, 587–594 (2023). https://doi.org/10.1007/s13318-023-00848-2
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DOI: https://doi.org/10.1007/s13318-023-00848-2