title: Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein.
abstract: The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.
authors.affiliation: Department of Pediatrics, Myongji Hospital, Seonam University College of Medicine , Goyang, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Biopharmaceutical Research Laboratoy, Dong-A Socio Holdings Research Institute , Gyeonggi, Republic of Korea.
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Kwak
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Medical Genetics, Ajou University Hospital , Suwon, Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Sohn
authors.affiliation: Department of Pediatrics, Jeil Hospital, Dankook University College of Medicine , Seoul, Republic of Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
authors.forename: Rimm
authors.initials: R
authors.lastname: Huh
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
authors.forename: Jinsup
authors.initials: J
authors.lastname: Kim
authors.affiliation: Clinical Research Center, Samsung Biomedical Research Institute , Seoul, Republic of Korea.
authors.forename: Ah-Ra
authors.initials: AR
authors.lastname: Ko
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: D000818:Animals; D006207:Half-Life; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007016:Hypophysectomy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017452:Receptors, IgG / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000494:pharmacology; D013977:Tibia / Q000254:growth & development; D015430:Weight Gain / Q000187:drug effects
chemical_list: D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D019382:Human Growth Hormone
keywords: Fc-domain of immunoglobulin G; pharmacodynamics; pharmacokinetics; recombinant human growth hormone