June 9, 2021
With the support of a five-year National Institutes of Health grant totaling $2,323,160, Daniel Gonzalez, Pharm.D., Ph.D., will work to characterize drug-drug interactions in infants.
Dedicated pharmacokinetic drug-drug interaction studies are performed in healthy adult volunteers during drug development. However, dedicated pharmacokinetic drug-drug interaction studies are rarely performed in infants due to ethical and logistical reasons, Gonzalez said.
This results in the extrapolation of adult drug dosing recommendations that account for the drug-drug interaction potential to infants despite known age-induced physiological changes that can alter pharmacokinetics and affect the drug-drug interaction magnitude in infants.
Gonzalez will work to evaluate a systematic approach to pharmacokinetic drug-drug interaction evaluation in infants using physiologically-based pharmacokinetic modeling and real-world data to accelerate the availability of age-appropriate drug dosing recommendations for infants in light of the drug-drug interaction potential.
The team will validate the physiologically-based pharmacokinetic model drug-drug interaction predictions using real-world data collected from infants receiving the drug combinations per standard of care.
“Physiologically-based pharmacokinetic models are an ideal tool to characterize pharmacokinetic drug-drug interactions in infants because they can account for the drug-drug interaction mechanism and physiological age-induced changes that affect the drug-drug interaction magnitude early in life,” said Gonzalez, an associate professor in the Division of Pharmacotherapy and Experimental Therapeutics at the UNC Eshelman School of Pharmacy, and adjunct in the Department of Pediatrics in the UNC School of Medicine.
Gonzalez will work with researchers from Duke University and the University of Waterloo on the project titled, “Application of Physiologically-Based Pharmacokinetic Modeling to Characterize Drug-Drug Interactions in Infants.” Team members will include Dr. Michael Cohen-Wolkowiez, Kiser-Arena Distinguished Professor of Pediatrics at Duke University; and Dr. Andrea Edginton, Professor, Hallman Director, and Associate Dean, Faculty of Science, at the University of Waterloo.
“Once our systematic approach to physiologically-based pharmacokinetic model informed drug-drug interaction evaluation in infants is established, it can be applied to characterize other pharmacokinetic drug-drug interactions and accelerate the availability of drug dosing recommendations for infants,” Gonzalez said.