title: Safety and biosimilarity of ior(®) EPOCIM compared with Eprex(®) based on toxicologic, pharmacodynamic, and pharmacokinetic studies in the Sprague-Dawley rat.
abstract: This study examined the safety, pharmacodynamic (PD), and pharmacokinetic (PK) biosimilarity of the human recombinant erythropoietin (EPO) products ior(®) EPOCIM and Eprex(®) following a 28-day repeated intravenous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 30, 300, and 600 I.U./kg of ior(®) EPOCIM or 600 I.U. of Eprex(®) . Adverse findings for both ior(®) EPOCIM and Eprex(®) were similar and were a consequence of thrombotic events (ulcerative skin lesions, swollen hock joints/lameness, stomach ulcers) and decreased body weight gains, all known adverse reactions to this class of drug in rats. With the exception of stomach ulcers, all other adverse findings were fully reversible. Neither drug stimulated the production of antidrug antibodies. As expected, ior(®) EPOCIM and Eprex(®) both increased reticulocyte, red blood cell, hemoglobin, and hematocrit levels in rats. The PK of EPO following dosing with ior(®) EPOCIM was well behaved and consistent with the literature. The results of this study imply that ior(®) EPOCIM and Eprex(®) had safety profiles, PD responses, and toxicokinetic profiles that were biosimilar.
authors.affiliation: Nucro-Technics, Toronto, Ontario, Canada, M1H 2W4.
authors.forename: Kresimir
authors.initials: K
authors.lastname: Pucaj
authors.affiliation: Nucro-Technics, Toronto, Ontario, Canada, M1H 2W4.
authors.forename: Katherine
authors.initials: K
authors.lastname: Riddle
authors.affiliation: Nucro-Technics, Toronto, Ontario, Canada, M1H 2W4.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Taylor
authors.affiliation: Centre of Molecular Immunology, CIMAB S.A., Atabey, Playa, Cuba. Electronic address: Nuris@cim.sld.cu.
authors.forename: Nuris
authors.initials: N
authors.lastname: Ledon
authors.affiliation: Nucro-Technics, Toronto, Ontario, Canada, M1H 2W4.
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Bolger
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D002626:Chemistry, Pharmaceutical; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D008297:Male; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D018570:Risk Assessment; D013810:Therapeutic Equivalency; D013927:Thrombosis / Q000139:chemically induced; D066007:Toxicokinetics; D015430:Weight Gain / Q000187:drug effects
chemical_list: D059451:Biosimilar Pharmaceuticals; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa
keywords: Eprex®; bioequivalence; biosimilar; erythropoietin; ior®EPOCIM; pharmacodynamic; pharmacokinetic; safety; toxicity; toxicokinetics