title: Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis.
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).
authors.affiliation: Clinical Pharmacology, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Linh M
authors.initials: LM
authors.lastname: Van
authors.forename: Andrej
authors.initials: A
authors.lastname: Skerjanec
authors.forename: David
authors.initials: D
authors.lastname: Floch
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Klein
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krammer
authors.forename: Gangadhar
authors.initials: G
authors.lastname: Sunkara
authors.forename: Dan
authors.initials: D
authors.lastname: Howard
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D015210:Arthritis, Gouty / Q000188:drug therapy / Q000378:metabolism*; D002097:C-Reactive Protein / Q000032:analysis; D004311:Double-Blind Method; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D000685:Serum Amyloid A Protein / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053583:Interleukin-1beta; D000685:Serum Amyloid A Protein; C541220:canakinumab; D002097:C-Reactive Protein
keywords: canakinumab; gouty arthritis patients; immunogenicity; pharmacodynamics; pharmacokinetics