Preclinical evaluation of a biobetter candidate: Pharmacokinetics and pharmacodynamics of GX‐G3 in healthy and neutropenia‐induced rats

• Published in: Drug development research 2019-09, Vol.80 (6), p.807-813
• Main Authors: Kim, Yun Jung, Ertan‐Ahmed, Senem, Capan, Yilmaz, Yang, Sang In
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic drugs; Antitumor agents; Bacterial infections; Colony-stimulating factor; Congenital defects; Fc‐fusion protein; Granulocyte Colony-Stimulating Factor - pharmacokinetics; Granulocyte Colony-Stimulating Factor - pharmacology; G‐CSF; G‐CSF‐hyFc; Half-Life; Infections; Infectious diseases; Injection; Injections, Subcutaneous; Leukocyte Count; Leukocytes (granulocytic); Leukocytes (neutrophilic); Male; Neutropenia; Neutropenia - immunology; Neutropenia - metabolism; Neutrophils - drug effects; Pharmacodynamics; pharmacokinetic pharmacodynamic; Pharmacokinetics; Pharmacology; Radiation therapy; Rats; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - pharmacology; Reduction; Vitamin B12; Vitamin deficiency
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21563

Neutropenia is a condition of an abnormally low number of neutrophils which render patients more susceptible to infections, especially to bacterial infections, as the condition may become life threatening and deadly without prompt medical attention. Various factors such as, anticancer drugs, radiotherapy, infectious diseases, congenital defects, or vitamin B12/B9 deficiency can trigger neutropenia. GX‐G3, a human hybrid (hy) Fc‐fused granulocyte colony stimulating factor (G‐CSF), was developed as next‐generation G‐CSF for the treatment of cancer therapy‐induced neutropenia. In this study, with the aim of investigating this promising potential next‐generation G‐CSF, comparative pharmacokinetic and pharmacodynamic studies were conducted in healthy and neutropenia‐induced rats. It was found that t1/2 of GX‐G3 is longer than same mass injection of filgrastim and pegfilgrastim and AUEClast (area under theeffect‐time curve from time zero to the last measurable ANC level) of absolute neutrophil count showed a significant increase after GX‐G3 injection compared with filgrastim and pegfilgrastim in healthy rats. Besides, in duration of neutropenia after the same mass injection GX‐G3 showed about 3.3 days of reduction effect compared with that of filgrastim, and 1.3 days of reduction effect compared with that of pegfilgrastim in neutropenia‐induced rats. These results demonstrate that the half‐life of GX‐G3 is longer than pegfilgrastim and GX‐G3 is more effective than filgrastim and pegfilgrastim in neutropenia‐induced rats.