We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis.
- Authors
Chakraborty, Abhijit; Van, Linh M.; Skerjanec, Andrej; Floch, David; Klein, Ulf R.; Krammer, Gerhard; Sunkara, Gangadhar; Howard, Dan
- Abstract
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).
- Subjects
ANALYSIS of covariance; BUTTER; CONFIDENCE intervals; ENZYME-linked immunosorbent assay; IMMUNOGENETICS; MONOCLONAL antibodies; PHARMACOKINETICS; RESEARCH funding; STRUCTURAL frame models; VISUAL analog scale; RECEIVER operating characteristic curves; DATA analysis software; DESCRIPTIVE statistics
- Publication
Journal of Clinical Pharmacology, 2013, Vol 53, Issue 12, p1240
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1002/jcph.162