Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD076676-01A1
Application #
8661919
Study Section
Special Emphasis Panel (ZRG1-EMNR-D (55))
Program Officer
Ren, Zhaoxia
Project Start
2014-08-01
Project End
2018-06-30
Budget Start
2014-08-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$621,379
Indirect Cost
$225,596

  Institution

Name
Duke University
Department
Other Clinical Sciences
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Maharaj, Anil R; Gonzalez, Daniel; Cohen-Wolkowiez, Michael et al. (2018) Improving Pediatric Protein Binding Estimates: An Evaluation of ?1-Acid Glycoprotein Maturation in Healthy and Infected Subjects. Clin Pharmacokinet 57:577-589
Autmizguine, Julie; Melloni, Chiara; Hornik, Christoph P et al. (2018) Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children. Antimicrob Agents Chemother 62:
Rivera-Chaparro, Nazario D; Ericson, Jessica; Wu, Huali et al. (2018) Safety, Effectiveness, and Exposure-Response of Micafungin in Infants: Application of an Established Pharmacokinetics Model to Electronic Health Records. Pediatr Infect Dis J :
Shakhnovich, Valentina; Brian Smith, P; Guptill, Jeffrey T et al. (2018) A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents. Paediatr Drugs 20:483-495
Ge, Shufan; Beechinor, Ryan J; Hornik, Christoph P et al. (2018) External Evaluation of a Gentamicin Infant Population Pharmacokinetic Model Using Data from a National Electronic Health Record Database. Antimicrob Agents Chemother 62:
Hornik, Christoph P; Gonzalez, Daniel; van den Anker, John et al. (2018) Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children. J Clin Pharmacol :
Hornik, Christoph P; Onufrak, Nikolas J; Smith, P Brian et al. (2018) Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants. Cardiol Young 28:85-92
Balevic, Stephen J; Cohen-Wolkowiez, Michael (2018) Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children. J Clin Pharmacol 58 Suppl 10:S58-S72
Dallefeld, Samantha H; Atz, Andrew M; Yogev, Ram et al. (2018) A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn 45:419-430
Le, Jennifer; Poindexter, Brenda; Sullivan, Janice E et al. (2018) Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates. Ther Drug Monit 40:103-108

Showing the most recent 10 out of 39 publications