Physiologically-based pharmacokinetic model to predict pharmacokinetics of KY0467 in humans and guide dose selection in infants and children
- 1Clinical Trial Center, Beijing Hospital, National Center for Gerontology, National Clinical Research Center for Gerontology, The Key Laboratory of Geriatrics of NHC, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Geriatrics-Based and AI-Driven Pharmaceutical and Medical Device Evaluation and Translation
Abstract
Background: Hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) remains a severe threat to infants and young children, with no specific antiviral therapy currently available. KY0467 is a novel EV71‐targeting antiviral drug under clinical development, but clinical data are limited to healthy adults, and appropriate pediatric dosing regimens are urgently needed.
Methods: In this study, a physiologically based pharmacokinetic (PBPK) model was developed and validated in rats and beagles, extrapolated to humans, and verified using clinical pharmacokinetic (PK) data from healthy adults. The model was then scaled to infants (28 days–23 months) and children (2–5 years) using age‐dependent physiological parameters to predict effective doses matching adult exposure at 30 mg/day.
Results: Predicted plasma concentration‐time profiles agreed well with observed values, and all mean fold errors (MFE) for T max , C max , and AUC 0‐t were within 0.5‐ to 2‐fold. Population simulations identified effective doses of 0.5 mg/kg/day for infants and 9 mg/day for children.
Conclusions: In conclusion, the adult PBPK model of KY0467 was successfully developed and validated for the first time, and the extrapolated pediatric model could be used to predict pediatric dosing of KY0467, which will provide invaluable references for the design of future clinical trials and its rational use in the pediatric population.
Related
- Physiologically based pharmacokinetic (PBPK) model to predict the magnitude of drug-drug interaction between vincristine and the azole antifungals isavuconazole, posaconazole, and voriconazole in children
- Physiologically Based Pharmacokinetic Modeling of Venetoclax in Pediatric Acute Myeloid Leukemia: Food Effects, Age-Related Pharmacokinetics, and Voriconazole-Mediated Drug-Drug Interactions.
- Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Aficamten in the Chinese Population.
- Introduction to Single‐Cell Physiologically‐Based Pharmacokinetic (scPBPK) Models
- Comprehensive comparison of six optimization algorithms for automated population pharmacokinetic model selection via two simulation studies and eleven real case studies
BibTeX
@article{xie2026physiologicallybased,
title = {{Physiologically-based pharmacokinetic model to predict pharmacokinetics of KY0467 in humans and guide dose selection in infants and children}},
author = {Panpan Xie and Yanyan Yang and Xuemei He and Ming Yang and Zhixing Chen and Xi Weng and Aixin Shi},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1866331},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1866331/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Physiologically-based pharmacokinetic model to predict pharmacokinetics of KY0467 in humans and guide dose selection in infants and children
AU - Panpan Xie
AU - Yanyan Yang
AU - Xuemei He
AU - Ming Yang
AU - Zhixing Chen
AU - Xi Weng
AU - Aixin Shi
PY - 2026
DA - 2026/10/12
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1866331
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1866331/full
AB - Background: Hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) remains a severe threat to infants and young children, with no specific antiviral therapy currently available. KY0467 is a novel EV71‐targeting antiviral drug under clinical development, but clinical data are limited to healthy adults, and appropriate pediatric dosing regimens are urgently needed. Methods: In this study, a physiologically based pharmacokinetic (PBPK) model was developed and validated in rats and beagles, extrapolated to humans, and verified using clinical pharmacokinetic (PK) data from healthy adults. The model was then scaled to infants (28 days–23 months) and children (2–5 years) using age‐dependent physiological parameters to predict effective doses matching adult exposure at 30 mg/day. Results: Predicted plasma concentration‐time profiles agreed well with observed values, and all mean fold errors (MFE) for T max , C max , and AUC 0‐t were within 0.5‐ to 2‐fold. Population simulations identified effective doses of 0.5 mg/kg/day for infants and 9 mg/day for children. Conclusions: In conclusion, the adult PBPK model of KY0467 was successfully developed and validated for the first time, and the extrapolated pediatric model could be used to predict pediatric dosing of KY0467, which will provide invaluable references for the design of future clinical trials and its rational use in the pediatric population.
SN - 1663-9812
ER -