title: Comparison of the pharmacokinetic and pharmacodynamic properties of two recombinant granulocyte colony-stimulating factor formulations after single subcutaneous administration to healthy volunteers.
abstract: OBJECTIVE
  The aim of this randomized, single dose, two-period crossover study with two weeks wash-out period was the demonstration of bioequivalence of two recombinant human granulocyte colony-stimulating factor (rG-CSF) formulations after subcutaneous administration of 300μg comparing their pharmacokinetic (primary endpoints AUC0-24, AUC0-∞ and Cmax) and pharmacodynamic (primary endpoints ANC AUC0-72, ANC AUC0-∞ and ANCmax) profiles in healthy male subjects.
  
  
  METHODS
  A total of 36 (23.0±6.0 years, 76.6±7.2kg) healthy subjects were recruited. Using a 1:1 randomization ratio, subjects were randomly assigned to one of two possible treatment-sequence groups to receive the single dose of test formulation (Gp-02) and reference product (Neupogen™) concentrations were measured by enzyme-linked immunosorbent assay (ELISA) up to 24h and the Absolute Neutrophil Count (ANC) was determined using hematology analyzer Coulter STKS™ (Beckman Coulter) up to 72h after injection. The geometric mean of primary pharmacokinetic and pharmacodynamic variables were considered bioequivalent if the 90% confidence intervals (CI) would fall in the bioequivalence range of 80%-125%.
  
  
  RESULTS
  AUC0-24 (ratio of means 103.4, 90% CI: 95.6-111.9), AUC0-∞ (103.4, 90% CI: 95.7-111.7), Cmax (99.6, 90% CI: 89.0-111.4), ANC AUC0-72 (100.0, 90% CI: 96.6-103.5), ANC AUC0-∞ (100.8, 90% CI: 96.5-105.3), and ANCmax (100.2, 90% CI: 95.4-105.1) were determined. Single doses of test and reference formulations were well tolerated. The incidence of AEs was equally distributed across treatment groups with the most frequent AEs being headache, fever, and back pain.
  
  
  CONCLUSIONS
  The study results demonstrated the bioequivalence of Gp-02, a new formulation of filgrastim, and the reference product Neupogen™.
authors.affiliation: Institute of Physiology and Pharmacology, Medicial Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania. Electronic address: audrius.sveikata@lsmuni.lt.
authors.forename: Audrius
authors.initials: A
authors.lastname: Sveikata
authors.affiliation: Institute of Physiology and Pharmacology, Medicial Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Gintautas
authors.initials: G
authors.lastname: Gumbrevičius
authors.affiliation: Institute of Physiology and Pharmacology, Medicial Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Kastytis
authors.initials: K
authors.lastname: Seštakauskas
authors.affiliation: Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Rima
authors.initials: R
authors.lastname: Kregždytė
authors.affiliation: Department of Applied Mathematics, Kaunas University of Technology, Kaunas, Lithuania.
authors.forename: Vytautas
authors.initials: V
authors.lastname: Janulionis
authors.affiliation: "Biomapas" UAB, Kaunas, Lithuania.
authors.forename: Vidmantas
authors.initials: V
authors.lastname: Fokas
mesh_terms: D000293:Adolescent; D000328:Adult; D006801:Humans; D008297:Male; D055815:Young Adult; D018592:Cross-Over Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000069585:Filgrastim / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D064368:Healthy Volunteers; D007279:Injections, Subcutaneous; D013810:Therapeutic Equivalency
chemical_list: D000069585:Filgrastim
keywords: Biosimilarity; Human granulocyte colony-stimulating factor; Pharmacodynamics; Pharmacokinetics; Safety