title: Comparative pharmacokinetic and pharmacodynamic evaluation between a new biosimilar and reference recombinant human growth hormone.
abstract: To extend available dosing options in the treatment of growth hormone deficiency, a comparative pharmacokinetic and pharmacodynamic phase-1 clinical study involving subcutaneous administration of growth hormone was conducted.
  
  
  
  The test formulation (biosimilar recombinant human growth hormone; r-hGH; Somatotropin) and reference formulation (Genotropin®) were tested in 38 adult healthy subjects after their subcutaneous administration of 12.8IU in an open label, single dose, randomized, two period cross over study separated with a washout period of 11days. Endogenous growth hormone release was suppressed by a continuous Octreotide infusion up to 24h after r-hGH administration. All the subjects were evaluated for local tolerance using Wong-Baker Faces pain rating scale and an injection site reaction (ISR) score. Detection of serum levels of r-hGH, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was done by suitable validated bio-analytical methods. Assessment of bioequivalence for pharmacokinetic parameters was done using log-transformed area under the curve (AUC) and maximum concentration (Cmax) for r-hGH. The pharmacodynamic assessment was done by comparing the area under the effect-time curve (AUEClast) and maximum measured effect concentration (Emax) of IGF-1 and IGFBP-3.
  
  
  
  The biosimilar formulation of recombinant human growth hormone fulfilled the predefined bioequivalence criteria for pharmacokinetic and pharmacodynamic parameters.
  
  
  
  The new biosimilar recombinant human growth hormone bears the potential to become an alternative option for the treatment of growth hormone deficiency.
authors.affiliation: Cristália Produtos Químicos Farmacêuticos, Ltda Highway Itapira-Lindóia, Km 14 - Ponte Preta, CEP: 13970-970 Itapira, SP, Brazil.
authors.forename: Odaly
authors.initials: O
authors.lastname: Toffoletto
authors.affiliation: Cristália Produtos Químicos Farmacêuticos, Ltda Highway Itapira-Lindóia, Km 14 - Ponte Preta, CEP: 13970-970 Itapira, SP, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Afiune
authors.affiliation: Cristália Produtos Químicos Farmacêuticos, Ltda Highway Itapira-Lindóia, Km 14 - Ponte Preta, CEP: 13970-970 Itapira, SP, Brazil.
authors.forename: Josef Ernst
authors.initials: JE
authors.lastname: Thiemann
authors.affiliation: Accutest Research Laboratories (I), Pvt. Ltd., A-31, M.I.D.C, T.T.C Industrial Area, Khairane, Navi Mumbai 400709, Maharashtra, India. Electronic address: suhas.khandave@accutestglobal.com.
authors.forename: Suhas S
authors.initials: SS
authors.lastname: Khandave
authors.affiliation: Accutest Biologics Pvt. Ltd., A-77, M.I.D.C, T.T.C Industrial Area, Khairane, Navi Mumbai 400709, Maharashtra, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Patel
authors.affiliation: Cristália Produtos Químicos Farmacêuticos, Ltda Highway Itapira-Lindóia, Km 14 - Ponte Preta, CEP: 13970-970 Itapira, SP, Brazil.
authors.forename: Debora G
authors.initials: DG
authors.lastname: Rodrigues
mesh_terms: D000328:Adult; D059451:Biosimilar Pharmaceuticals / Q000494:pharmacology*; D005260:Female; D064368:Healthy Volunteers; D019382:Human Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D059451:Biosimilar Pharmaceuticals; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: Bioequivalence; Biosimilar; Genotropin; Human growth hormone; r-hGH