Physiologically Based Pharmacokinetic Prediction of Linezolid and Emtricitabine in Neonates and Infants.
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.



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.



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).



These results suggest that PBPK modeling may provide one option to help predict the pharmacokinetics of renally excreted drugs in neonates and infants.
Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.
Peng
P
Duan
National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, 72079, USA.
Jeffrey W
JW
Fisher
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Building 51, Rm 2154, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.
Kenta
K
Yoshida
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Building 51, Rm 2154, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.
Lei
L
Zhang
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Building 51, Rm 2154, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.
Gilbert J
GJ
Burckart
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Building 51, Rm 2154, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA. jian.wang@fda.hhs.gov.
Jian
J
Wang
D061605:Administration, Intravenous; D000284:Administration, Oral; D000367:Age Factors; D000068679:Emtricitabine / Q000493:pharmacokinetics*; D005544:Forecasting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D000069349:Linezolid / Q000493:pharmacokinetics*; D008954:Models, Biological
D000068679:Emtricitabine; D000069349:Linezolid