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Ciliary neurotrophic factor: Pharmacokinetics and acute‐phase response in rat
Author(s) -
Dittrich Falk,
Theonen Hans,
Sendtner Michael
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410350206
Subject(s) - ciliary neurotrophic factor , pharmacokinetics , in vivo , skeletal muscle , pharmacology , medicine , endocrinology , neurotrophic factors , chemistry , receptor , biology , microbiology and biotechnology
Ciliary neurotrophic factor (CNTF) supports the survival of motoneurons in vitro and in vivo. Recombinant CNTF is an investigational drug for the treatmentof amyotrophic lateral sclerosis. We determined the pharmacokinetics of radioiodinated CNTF after intravenous injection into rats. CNTF shows a biphasic clearance with an initial plasma half‐life of 2.9 minutes and is removed from the circulation by the liver. No accumulation of radioactivity was detectable in nerve tissue or skeletal muscle after intravenous injection of 0.1 μg and 0.5 μg of CNTF. Radioactive degradation products accumulate in the skin. Liver cells express specific binding proteins for CNTF, and the incorporation and degradation of intravenously injected CNTF by the liver may occur after association of CNTF with the soluble CNTF receptor α in the circulation. Probably as a consequence of its binding to hepatocytes, CNTF induces acute‐phase responses in liver. The short half‐life and the inflammatory side effect may limit the clinical usefulness of systematically administered CNTF in the treatment of human motoneuron disorders.