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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.

Author information

1
SGS Exprimo NV, Generaal de Wittelaan 19A Bus 5, Mechelen, Belgium.
2
UCB Ltd, Slough, Berkshire, England.
3
UCB, Research Triangle Park, NC, USA.
4
The University of Western Ontario, London, Ontario, Canada.
5
Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.

Abstract

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.

KEYWORDS:

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

PMID:
25735646
PMCID:
PMC6680228
DOI:
10.1002/jcph.491
[Indexed for MEDLINE]
Free PMC Article

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