PMID- 26370910
OWN - NLM
STAT- MEDLINE
DCOM- 20160906
LR  - 20151005
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 12
IP  - 10
DP  - 2015 Oct 5
TI  - Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human 
      Growth Hormone: Fc Fusion Protein.
PG  - 3759-65
LID - 10.1021/acs.molpharmaceut.5b00550 [doi]
AB  - 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 mug/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.
FAU - Kim, Su Jin
AU  - Kim SJ
AD  - Department of Pediatrics, Myongji Hospital, Seonam University College of Medicine 
      , Goyang, Republic of Korea.
FAU - Kwak, Hyun-Hee
AU  - Kwak HH
AD  - Biopharmaceutical Research Laboratoy, Dong-A Socio Holdings Research Institute , 
      Gyeonggi, Republic of Korea.
FAU - Cho, Sung Yoon
AU  - Cho SY
AD  - Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine , Seoul, Republic of Korea.
FAU - Sohn, Young Bae
AU  - Sohn YB
AD  - Department of Medical Genetics, Ajou University Hospital , Suwon, Republic of 
      Korea.
FAU - Park, Sung Won
AU  - Park SW
AD  - Department of Pediatrics, Jeil Hospital, Dankook University College of Medicine , 
      Seoul, Republic of Korea.
FAU - Huh, Rimm
AU  - Huh R
AD  - Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine , Seoul, Republic of Korea.
FAU - Kim, Jinsup
AU  - Kim J
AD  - Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine , Seoul, Republic of Korea.
FAU - Ko, Ah-Ra
AU  - Ko AR
AD  - Clinical Research Center, Samsung Biomedical Research Institute , Seoul, Republic 
      of Korea.
FAU - Jin, Dong-Kyu
AU  - Jin DK
AD  - Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine , Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20150921
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Receptors, IgG)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 12629-01-5 (Human Growth Hormone)
SB  - IM
MH  - Animals
MH  - Half-Life
MH  - Human Growth Hormone/*analogs & derivatives/pharmacokinetics/pharmacology
MH  - Humans
MH  - Hypophysectomy
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, IgG/*metabolism
MH  - Recombinant Fusion Proteins/*pharmacokinetics/pharmacology
MH  - Tibia/growth & development
MH  - Weight Gain/drug effects
OTO - NOTNLM
OT  - Fc-domain of immunoglobulin G
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - recombinant human growth hormone
EDAT- 2015/09/16 06:00
MHDA- 2016/09/07 06:00
CRDT- 2015/09/16 06:00
PHST- 2015/09/16 06:00 [entrez]
PHST- 2015/09/16 06:00 [pubmed]
PHST- 2016/09/07 06:00 [medline]
AID - 10.1021/acs.molpharmaceut.5b00550 [doi]
PST - ppublish
SO  - Mol Pharm. 2015 Oct 5;12(10):3759-65. doi: 10.1021/acs.molpharmaceut.5b00550. 
      Epub 2015 Sep 21.