title: A pharmacokinetic and pharmacodynamic comparison of a novel pegylated recombinant consensus interferon-α variant with peginterferon-α-2a in healthy subjects.
abstract: OBJECTIVE
  The aims of the study were to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of a novel, pegylated recombinant human consensus interferon-α variant (PEG-IFN-SA) in healthy volunteers. A pharmacokinetic and pharmacodynamic comparison of PEG-IFN-SA and peginterferon-α-2a in healthy subjects was evaluated.
  
  
  METHODS
  A randomized, dose-escalating, single administration dose phase I clinical study was conducted. Thirty healthy subjects received PEG-IFN-SA as a single dose of 0.5-2.0 μg kg(-1) by subcutaneous (s.c.) injection in four parallel groups. Eight subjects received peginterferon-α-2a as a single dose of 180 μg s.c.
  
  
  RESULTS
  The incidence rates of adverse events for PEG-IFN-SA and peginterferon-α-2a were 29 of 30 and 7 of 8, respectively. The adverse events for PEG-IFN-SA were mild to moderate and similar to those of peginterferon-α-2a. Within 168 h after injection, the mean values of maximal concentration and area under the plasma concentration-time curve from time of dosing to 168 h [AUC(0-168h) ] for 2',5'-oligoadenylate, neopterin and β2 -microglobulin for PEG-IFN-SA at 1.5 μg kg(-1 ) s.c. were similar to or higher than those for peginterferon-α-2a at a dose of 180 μg s.c. After s.c. injection of PEG-IFN-SA at 1.5 μg kg(-1) , the mean geometric mean values of plasma half-life, time to maximal concentration, maximal concentration and AUC(0-168h) were 55.3 h, 26.9 h, 0.53 μg l(-1) and 44.0 μg l(-1)  h, respectively.
  
  
  CONCLUSIONS
  The tolerance, pharmacokinetic and pharmacodynamic characteristics of PEG-IFN-SA support its administration by s.c. injection as a single dose of 1.5 μg kg(-1) or at 2.0 μg kg(-1) per week.
authors.affiliation: Institute of Clinical Pharmacology/GCP Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Mao Ping
authors.initials: MP
authors.lastname: Li
authors.forename: Zhong Ping
authors.initials: ZP
authors.lastname: Gou
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Xu
authors.forename: Yong Ming
authors.initials: YM
authors.lastname: Cai
authors.forename: Hua
authors.initials: H
authors.lastname: Luo
mesh_terms: D000227:Adenine Nucleotides / Q000097:blood / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000276:immunology; D009843:Oligoribonucleotides / Q000097:blood / Q000276:immunology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D000998:Antiviral Agents; D016898:Interferon-alpha; D009843:Oligoribonucleotides; C571406:PEG-IFN-SA; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C023505:2',5'-oligoadenylate; D019798:Neopterin; C100416:peginterferon alfa-2a
keywords: PEG-IFN-SA; pharmacodynamics; pharmacokinetics; safety; tolerability