Scientific Publications by FDA Staff

Clin Pharmacokinet 2017 Apr;56(4):383-94

Physiologically based pharmacokinetic prediction of linezolid and emtricitabine in neonates and infants.

Duan P, Fisher JW, Yoshida K, Zhang L, Burckart GJ, Wang J

INTRODUCTION: Modeling and simulation approaches are increasingly being utilized in pediatric drug development. Physiologically based pharmacokinetic (PBPK) modeling offers an enhanced ability to predict age-related changes in pharmacokinetics in the pediatric population. METHODS: In the current study, adult PBPK models were developed for the renally excreted drugs linezolid and emtricitabine. PBPK models were then utilized to predict pharmacokinetics in pediatric patients for various age groups from the oldest to the youngest patients in a stepwise approach. RESULTS: Pharmacokinetic predictions for these two drugs in the pediatric population, including infants and neonates, were within a twofold range of clinical observations. Based on this study, linezolid and emtricitabine pediatric PBPK models incorporating the ontogeny in renal maturation describe the pharmacokinetic differences between adult and pediatric populations, even though the contribution of renal clearance to the total clearance of two drugs was very different (30 % for linezolid vs. 86 % for emtricitabine). CONCLUSION: These results suggest that PBPK modeling may provide one option to help predict the pharmacokinetics of renally excreted drugs in neonates and infants.