Open AccessPharmacokinetics and Pharmacological Effect of Recombinant Human Granulocyte Colony‐stimulating Factor Conjugated to Poly(styrene‐co‐maleic acid) in Rats
Author(s) -
Kunimasa JunIchi,
Itoga Yoshie,
Yasuhara Masato,
Hori Ryohei,
Inui KenIchi
Publication year - 1999
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/0022357991773131
Subject(s) - maleic acid , styrene , granulocyte , bovine serum albumin , chemistry , biochemistry , copolymer , biology , immunology , organic chemistry , polymer
A new derivative of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) has been synthesized by conjugating rhG‐CSF to poly(styrene‐co‐maleic acid) (poly(styrene‐co‐maleic acid)‐rhG‐CSF) to try to avoid glomerular filtration and thus potentiate the neutrophil‐proliferating activity of rhG‐CSF. Poly(styrene‐co‐maleic acid)‐rhG‐CSF was highly bound to bovine serum albumin (BSA) and the molecular weight of the poly(styrene‐co‐maleic acid)‐rhG‐CSF‐BSA complex was estimated to be about 90 000 by gel filtration. Intravenous administration of poly(styrene‐co‐maleic acid)‐rhG‐CSF to normal rats resulted in a dose‐dependent increase in neutrophil count. The neutrophil‐proliferating activity of poly(styrene‐co‐maleic acid)‐rhG‐CSF was about 10 times greater than that of rhG‐CSF. After intravenous injection at a dose of 5 protein kg −1 , the total clearance of rhG‐CSF fell from 71.0 to 32.1mL h −1 kg −1 following poly(styrene‐co‐maleic acid) modification. An isolated perfusion study in rat kidney showed that the filtered fraction of rhG‐CSF was reduced by conjugation with poly(styrene‐co‐maleic acid). These results suggest that poly(styrene‐co‐maleic acid)‐conjugation can potentiate the neutrophil‐proliferating activity of rhG‐CSF by reducing, at least in part, its renal clearance.