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J Clin Pharmacol. 2015 Aug;55(8):866-74. doi: 10.1002/jcph.491. Epub 2015 Apr 13.

Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease.

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SGS Exprimo NV, Generaal de Wittelaan 19A Bus 5, Mechelen, Belgium.
UCB Ltd, Slough, Berkshire, England.
UCB, Research Triangle Park, NC, USA.
The University of Western Ontario, London, Ontario, Canada.
Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.


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.


Crohn's disease; NONMEM; anti-TNF; certolizumab pegol; covariates

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