Pharmacokinetics and C-reactive protein modelling of anti-interleukin-6 antibody (PF-04236921) in healthy volunteers and patients with autoimmune disease

British Journal of Clinical Pharmacology
Cheryl LiJean Beebe

Abstract

The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-interleukin-6 monoclonal antibody, and its pharmacokinetic/pharmacodynamic (PK/PD) relationship on serum C-reactive protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Crohn's disease (CD). Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from two phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study and a Phase 2 SLE study were included. A two-compartment model with first order absorption and linear elimination and a mechanism-based indirect response model adequately described the PK and PK/PD relationships, respectively. Central compartment volume of distribution (Vc) positively correlated with body weight. Clearance (CL) negatively correlated with baseline albumin concentration and positively correlated with baseline CRP and creatinine clearance, and was slightly lower in females. After correcting for covariates, CL in CD subjects was approximately 60% higher than other populations. Maximum inhibition of PF-04236921 on CRP production (Imax ) negatively correlated with baseline albumin. Imax positively ...Continue Reading

References

Jul 1, 1997·Nature Biotechnology·V GhetieE S Ward
Oct 17, 2003·Current Drug Targets. Inflammation and Allergy·Hiroaki Ito
Mar 6, 2004·Journal of Pharmacokinetics and Pharmacodynamics·Liping ZhangLewis B Sheiner
Jun 24, 2004·Computer Methods and Programs in Biomedicine·Lars LindbomE Niclas Jonsson
Sep 25, 2004·Journal of Pharmaceutical Sciences·Evelyn D LoboJoseph P Balthasar
Oct 9, 2004·Inflammatory Bowel Diseases·Séverine VermeirePaul Rutgeerts
Dec 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul R HintonNaoya Tsurushita
May 22, 2008·The Journal of Clinical Endocrinology and Metabolism·Jean-François MaugerBenoît Lamarche
Sep 12, 2008·Clinical Pharmacology and Therapeutics·W WangJ P Balthasar
Aug 4, 2009·The AAPS Journal·Radojka M Savic, Mats O Karlsson
Sep 17, 2009·European Journal of Clinical Pharmacology·Adedigbo A FasanmadeHonghui Zhou
Feb 25, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thomas PuchalskiHugh M Davis
Jul 9, 2010·Clinical Pharmacokinetics·Ron J KeizerJos H Beijnen
Sep 8, 2010·Clinical Pharmacokinetics·Nathanael L Dirks, Bernd Meibohm
Feb 9, 2011·The AAPS Journal·Martin BergstrandMats O Karlsson
Jul 12, 2011·Inflammatory Bowel Diseases·Serena CatarziTeresa Iantomasi
Feb 24, 2012·Clinical Pharmacology and Therapeutics·Ingrid OrdásWilliam J Sandborn
Nov 28, 2015·British Journal of Clinical Pharmacology·E Niclas JonssonRosalin H Arends
Jan 29, 2016·Clinical Pharmacokinetics·Katherine L GillManoranjenni Chetty
Nov 20, 2016·Gut·Pablo OliveraLaurent Peyrin-Biroulet
Oct 22, 2017·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators

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