Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis

Pharmacokinetics and pharmacodynamics of the anti‐interleukin (IL)‐1β monoclonal antibody, canakinumab, in gouty arthritis patients from three studies are reported. Canakinumab has low serum clearance (0.214 L/day), low steady‐state volume of distribution (7.44 L), a 25.8‐day half‐life, and approxim...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2013-12, Vol.53 (12), p.1240-1251
Main Authors: Chakraborty, Abhijit, Van, Linh M., Skerjanec, Andrej, Floch, David, Klein, Ulf R., Krammer, Gerhard, Sunkara, Gangadhar, Howard, Dan
Format: Article
Language:English
Subjects:
Adult
Antibodies, Monoclonal - blood
Antibodies, Monoclonal - pharmacology
Arthritis
Arthritis, Gouty - drug therapy
Arthritis, Gouty - metabolism
C-Reactive Protein - analysis
canakinumab
Double-Blind Method
gouty arthritis patients
Humans
immunogenicity
Interleukin-1beta - antagonists & inhibitors
Interleukin-1beta - metabolism
Middle Aged
Models, Biological
pharmacodynamics
pharmacokinetics
Serum Amyloid A Protein - analysis
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Summary:Pharmacokinetics and pharmacodynamics of the anti‐interleukin (IL)‐1β monoclonal antibody, canakinumab, in gouty arthritis patients from three studies are reported. Canakinumab has low serum clearance (0.214 L/day), low steady‐state volume of distribution (7.44 L), a 25.8‐day half‐life, and approximately 60% subcutaneous absolute bioavailability in a typical 93‐kg patient. Creatinine clearance had a small positive impact on serum canakinumab clearance that is not likely to be clinically relevant. Binding to circulating IL‐1β was demonstrated by increases in total serum IL‐1β following canakinumab dosing. Total IL‐1β kinetics and canakinumab pharmacokinetics were characterized by a population‐based pharmacokinetic‐binding model, where the estimated apparent in vivo dissociation constant (signifying binding affinity of canakinumab to circulating IL‐1β) was 0.99 nmol/L in gouty arthritis patients. Canakinumab treatment provided rapid, sustained decreases in C‐reactive protein and serum amyloid A, provided superior pain relief to triamcinolone acetonide, and increased time to first recurrent attack (P ≤ 0.01 favoring all canakinumab doses vs. triamcinolone acetonide).
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.162