Chakraborty, Abhijit, Van, Linh, Skerjanec, Andrej, Floch, David, Klein, Ulf, Krammer, Gerhard, Sunkara, Gangadhar and Howard, Danny (2013) Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis. Journal of Clinical Pharmacology, 53 (12). pp. 1240-1251. ISSN 0091-2700

Abstract

Pharmacokinetics and pharmacodynamics of the anti ]interleukin (IL)]1b 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]1b was demonstrated by increases in total serum IL]1b following canakinumab dosing. Total IL]1b 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]1b) 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 (P0.01 favoring all canakinumab doses vs. triamcinolone acetonide). © 2013, The American College of Clinical Pharmacology.

Item Type:	Article
Keywords:	Canakinumab Gouty arthritis patients Immunogenicity Pharmacodynamics Pharmacokinetics
Date Deposited:	21 Nov 2017 00:45
Last Modified:	25 Jan 2019 00:46
URI:	https://oak.novartis.com/id/eprint/10083