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Understanding the pharmacokinetic journey of Fc-fusion protein, rhIL-7-hyFc using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA.
Kim, Anhye; Oh, Min-Seok; Lee, Gwan-Ho; Song, Seongeun; Byun, Mi-Sun; Choi, Donghoon; Yu, Byung-Yong; Lee, Howard.
Afiliação
  • Kim A; Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea.
  • Oh MS; Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam 13488, Republic of Korea.
  • Lee GH; Institute for Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam 13488, Republic of Korea.
  • Song S; Research Resources Division, Advanced Analysis and Data Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
  • Byun MS; Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea.
  • Choi D; Research Resources Division, Advanced Analysis and Data Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
  • Yu BY; Research Resources Division, Advanced Analysis and Data Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
  • Lee H; Department of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea.
Antib Ther ; 7(2): 105-113, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38566969
ABSTRACT
Antibody-based therapeutics (ABTs), including monoclonal/polyclonal antibodies and fragment crystallizable region (Fc)-fusion proteins, are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS). Totally, four rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14C-rhIL-7-hyFc, which was prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. The TRA concentrations in organs were determined by AMS. Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. The rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed an elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc's affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method. Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offers valuable insights for the development and optimization of ABT.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article