The majority of off-patent drugs prescribed to children lack dosing information specific to this population, which can result in treatment failures and toxicities. Dosing information is lacking because clinical trials involving children pose specific challenges, among the most important of which is the large number of children required to estimate appropriate dosing at every stage of child development. Population physiologically based pharmacokinetic (PBPK) models are mathematical tools that incorporate changes of childhood, along with drug characteristics and genetic variances, to find the most appropriate dose for every pediatric age. By incorporating these factors, PBPK models can reduce the number of children needed for clinical trials. This proposal will systematically develop, and prospectively validate, population PBPK modeling in children.
Enrolling children in clinical trials to establish the safest and most efficacious dose of commonly used drugs is challenging. This proposal will evaluate a mathematical tool, population physiologically-based pharmacokinetic models, to reduce the number of children enrolled in clinical trials without compromising the quality of dosing information.
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|Ericson, Jessica E; Zimmerman, Kanecia O; Gonzalez, Daniel et al. (2017) A Systematic Literature Review Approach to Estimate the Therapeutic Index of Selected Immunosuppressant Drugs After Renal Transplantation. Ther Drug Monit 39:13-20|
|Smith, Michael J; Gonzalez, Daniel; Goldman, Jennifer L et al. (2017) Pharmacokinetics of Clindamycin in Obese and Nonobese Children. Antimicrob Agents Chemother 61:|
|Gonzalez, Daniel; Chamberlain, James M; Guptill, Jeffrey T et al. (2017) Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus. Clin Pharmacokinet 56:941-951|
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|Wang, Laura A; Gonzalez, Daniel; Leeder, J Steven et al. (2017) Metronidazole Metabolism in Neonates and the Interplay Between Ontogeny and Genetic Variation. J Clin Pharmacol 57:230-234|
|Rivera-Chaparro, Nazario D; Cohen-Wolkowiez, Michael; Greenberg, Rachel G (2017) Dosing antibiotics in neonates: review of the pharmacokinetic data. Future Microbiol 12:1001-1016|
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