Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease. (13th April 2015)

• Record Type: Journal Article
• Authors: Wade, Janet R.; Parker, Gerry; Kosutic, Gordana; Feagen, Brian G.; Sandborn, William J.; Laveille, Christian; Oliver, Ruth
• Is Part Of: Journal of clinical pharmacology. Volume 55:Number 8(2015:Aug.)
• Page Start: 866
• Page End: 874
• Publication Date: 2015-04-13
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.491
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcph491-sec-0001" sec-type="section"> <p>Certolizumab pegol (CZP), an anti–tumor necrosis factor α agent, is an effective therapy for Crohn's disease (CD). A population pharmacokinetic (PK) analysis of subcutaneously administered CZP was performed using data from 2157 CD patients from 9 separate studies. The aim was to determine which covariates influence the disposition of CZP. The final CZP population PK model consisted of a baseline, first‐order absorption, and 1‐compartment disposition. CZP antibodies were treated as a structural model covariate and caused apparent clearance (CL/F) to increase from 0.685 to 2.74 L/day. Body surface area (BSA) influenced both CL/F and apparent volume of distribution (V/F) in a linear fashion; both parameters increased by more than 53% and 49%, respectively, across the range of BSA measurements in the data. Albumin influenced CZP CL/F in a nonlinear fashion; CL/F decreased from 1.05 to 0.613 L/day with increasing albumin concentrations in antibody‐negative patients. C‐reactive protein (CRP) had a borderline influence and CL/F increased by more than 20% across the range of CRP measurements in the data set. Race had a minor influence on V/F. The determined covariates' impact on CZP disposition may be of clinical utility in CZP therapy of CD patients when the PK/pharmacodynamic relationship becomes available.</p> </sec> </abstract>