title: Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children.
abstract: OBJECTIVE
  Recombinant human growth hormone (rhGH) replacement therapy in children generally requires daily subcutaneous (sc) injections, which may be inconvenient for patients. Jintrolong® is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong® vs daily doses of rhGH.
  
  
  METHODS
  Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong® at 0.2 mg/kg/w.
  
  
  RESULTS
  In comparison with rhGH, sc injection of Jintrolong® produced a noticeably higher C max, significantly longer half-life (t 1/2), and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC) after the seventh and first injections (AUC(0-∞)7th/AUC(0-∞)1st) of rhGH was 1.02, while the AUC(0-∞)6th/AUC(0-∞)1st of Jintrolong ® was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong® injections. There were no severe adverse events during the trial.
  
  
  CONCLUSIONS
  The elimination rate of Jintrolong® was slower than that of sc rhGH. No progressive serum accumulation of Jintrolong® was found. The changes in insulin-like growth factor-1 expression produced by rhGH and Jintrolong® were comparable, indicating similar pharmacodynamics. Our results demonstrate that Jintrolong® is suitable for long-term growth hormone treatment in children with growth hormone deficiency.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Pharmacy, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China.
authors.forename: Zhi-Hang
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China.
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Luo
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006207:Half-Life; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency / Q000493:pharmacokinetics; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins
chemical_list: D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I
keywords: long-acting growth hormone; multiple-dose; phase I