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.

Public Health Relevance

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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-EMNR-D (55))
Program Officer
Ren, Zhaoxia
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Duke University
Other Clinical Sciences
Schools of Medicine
United States
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Salerno, Sara; Hornik, Christoph P; Cohen-Wolkowiez, Michael et al. (2017) Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin-Tazobactam Safety in Infants. Pediatr Infect Dis J 36:855-859
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
Hornik, Christoph P; Wu, Huali; Edginton, Andrea N et al. (2017) Development of a Pediatric Physiologically-Based Pharmacokinetic Model of Clindamycin Using Opportunistic Pharmacokinetic Data. Clin Pharmacokinet 56:1343-1353
Watt, Kevin M; Cohen-Wolkowiez, Michael; Williams, Duane C et al. (2017) Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit. J Extra Corpor Technol 49:150-159
Gonzalez, Daniel; Bradley, John S; Blumer, Jeffrey et al. (2017) Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age. Pediatr Infect Dis J 36:645-653
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
Maharaj, Anil R; Gonzalez, Daniel; Cohen-Wolkowiez, Michael et al. (2017) Improving Pediatric Protein Binding Estimates: An Evaluation of ?1-Acid Glycoprotein Maturation in Healthy and Infected Subjects. Clin Pharmacokinet :

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