TY - JOUR
T1 - The pharmacokinetics of subcutaneously administered recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis
T2 - Relation to parameters of the acute-phase response
AU - Cedarbaum, J. M.
AU - Chapman, C.
AU - Charatan, M.
AU - Stambler, N.
AU - Andrews, L.
AU - Zhan, C.
AU - Radka, S.
AU - Morrisey, D.
AU - Lakings, D.
AU - Brooks, B. R.
AU - Sanjak, M.
AU - Pestronk, A.
AU - Florence, J.
AU - Mitsumoto, H.
AU - Szirony, K.
AU - Bittle, L.
AU - Ringel, S.
AU - Neville, H.
AU - Brinkmann, J.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - Amytrophic lateral sclerosis
KW - Ciliary neurotrophic factor
KW - rHCNTF
UR - http://www.scopus.com/inward/record.url?scp=0028863291&partnerID=8YFLogxK
U2 - 10.1097/00002826-199512000-00003
DO - 10.1097/00002826-199512000-00003
M3 - Article
C2 - 8681311
AN - SCOPUS:0028863291
SN - 0362-5664
VL - 18
SP - 500
EP - 514
JO - Clinical Neuropharmacology
JF - Clinical Neuropharmacology
IS - 6
ER -