Asia Pacific Journal of Pediatric and Child Health

Original research

Ref Number: APCP-RP-127

Pharmacokinetic/Pharmacodynamic Analysis of Long-Acting PEGylated Recombinant Human Growth Hormone in Children with Idiopathic Short Stature

Xiao-Ping Luo¹, Chun-Xiu Gong², Jun-Fen Fu³, Yu Yang⁴, Chun-Lin Wang⁵, Fei-Hong Luo⁶, Rui-Min Chen⁷, Ling Hou¹, Zhe Su⁸, Xiang-Lan Wen⁹

1- Tongji Medical College, Huazhong University of Science & Technology, China 2- Beijing Children’s Hospital, Capital Medical University, China 3- National Clinical Research Center for Children and Adolescents' Health and Diseases, Hangzhou, China 4- Jiangxi Provincial Children's Hospital, Nanchang, China 5- The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China 6- Children’s Hospital of Fudan University, Shanghai, China 7- Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, China 8- Shenzhen Children’s Hospital, Shenzhen, China 9- Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Zhuzhou, China

Corresponding Author: Xiao-Ping Luo (xpluo@tjh.tjmu.edu.cn )

Abstract Body

Introduction: Idiopathic short stature (ISS) is a common cause of pediatric short stature, accounting for 60–80% of pediatric short stature cases. Long-acting PEGylated recombinant human growth hormone (PEG-rhGH) has been approved for ISS, but its dose–exposure–response relationship remains unclear. Objectives: This study aimed to develop a population PK/PD model for PEG-rhGH in children with ISS using quantitative pharmacology and to characterize the dose–exposure–response relationship. Methods: Data from three studies were integrated: a sparse PK/PD sampling study (NCT03221088; n=360), a retrospective–prospective cohort (NCT06110910; n=1,168), and a dose-ranging study (ChiCTR2400087245; n=101). Direct bridging (external validation of a GHD model) and indirect bridging (joint population modeling) were performed using NONMEM. Exposure–response analyses evaluated height velocity (HV) and height SDS (HTSDS). Results: The ISS PopPK/PD model exhibited adequate goodness-of-fit, as evidenced by the good agreement between observed and predicted values and the uniform distribution of residuals. HV was driven by ΔIGF-1 SDS (β=0.33, p

Keywords: Recombinant human growth; Htsds; Model

Presentation Type: Original research