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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Wang, Laura A; Cohen-Wolkowiez, Michael; Gonzalez, Daniel (2016) Advances in Pediatric Pharmacology, Therapeutics, and Toxicology. Adv Pediatr 63:227-54
Gonzalez, Daniel; Palazzi, Debra L; Bhattacharya-Mithal, Leena et al. (2016) Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents. Antimicrob Agents Chemother 60:2572-6
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Gonzalez, Daniel; Delmore, Paula; Bloom, Barry T et al. (2016) Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother 60:2888-94
Greenberg, Rachel G; Melloni, Chiara; Wu, Huali et al. (2016) Therapeutic Index Estimation of Antiepileptic Drugs: A Systematic Literature Review Approach. Clin Neuropharmacol 39:232-40
Zimmerman, Kanecia O; Wu, Huali; Greenberg, Rachel et al. (2016) Therapeutic Drug Monitoring, Electronic Health Records, and Pharmacokinetic Modeling to Evaluate Sirolimus Drug Exposure-Response Relationships in Renal Transplant Patients. Ther Drug Monit 38:600-6
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Gonzalez, Daniel; Melloni, Chiara; Poindexter, Brenda B et al. (2015) Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots. Bioanalysis 7:1137-49

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