The pharmacokinetics of subcutaneously administered recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis: Relation to parameters of the acute-phase response

J. M. Cedarbaum, C. Chapman, M. Charatan, N. Stambler, L. Andrews, C. Zhan, S. Radka, D. Morrisey, D. Lakings, B. R. Brooks, M. Sanjak, A. Pestronk, J. Florence, H. Mitsumoto, K. Szirony, L. Bittle, S. Ringel, H. Neville, J. Brinkmann

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Abstract

Fifty-seven patients with amyotrophic lateral sclerosis (ALS) were randomly assigned to receive single subcutaneous doses of 0.5, 1, 3, 7, 10, or 30 μg/kg recombinant human ciliary neurotrophic factor (rHCNTF) or placebo. Peak plasma concentrations occurred 180 to 260 min after dosing. rHCNTF plasma concentrations then appeared to decay, with an apparent elimination half-life of 120-400 min. Eight of 12 patients who received the highest dose had measurable plasma rHCNTF levels 24 h after dosing. Peak plasma concentrations of rHCNTF in patients receiving 30 μg/kg rHCNTF were in the range that has been shown to support the survival of embryonic rat and human motor neurons in tissue culture. Systemic exposure to rHCNTF increased with increasing dose. The elimination of rHCNTF, over the dose range evaluated, appeared to follow first-order processes. Elevations in body temperature and evidence of activation of the acute phase response were observed.

Original languageEnglish
Pages (from-to)500-514
Number of pages15
JournalClinical Neuropharmacology
Volume18
Issue number6
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • Amytrophic lateral sclerosis
  • Ciliary neurotrophic factor
  • rHCNTF

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    Cedarbaum, J. M., Chapman, C., Charatan, M., Stambler, N., Andrews, L., Zhan, C., Radka, S., Morrisey, D., Lakings, D., Brooks, B. R., Sanjak, M., Pestronk, A., Florence, J., Mitsumoto, H., Szirony, K., Bittle, L., Ringel, S., Neville, H., & Brinkmann, J. (1995). The pharmacokinetics of subcutaneously administered recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis: Relation to parameters of the acute-phase response. Clinical Neuropharmacology, 18(6), 500-514. https://doi.org/10.1097/00002826-199512000-00003