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

Journal of Clinical Pharmacology
Janet R WadeRuth Oliver

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...Continue Reading

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Citations

Aug 5, 2016·Journal of Crohn's & Colitis·Vipul JairathBrian G Feagan
Aug 6, 2016·Current Medical Research and Opinion·Gil Y MelmedWilliam J Sandborn
Oct 22, 2016·Expert Review of Clinical Pharmacology·Divya SamineniChunze Li
Nov 22, 2017·Alimentary Pharmacology & Therapeutics·N Vande CasteeleW J Sandborn
Feb 21, 2018·Journal of Clinical Pharmacology·Hannah HoseyniHonghui Zhou
Mar 8, 2018·Clinical Pharmacokinetics·Luc J J DerijksAdriaan A van Bodegraven
Sep 18, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Faizan MazharCarla Carnovale
Aug 28, 2019·Clinical Pharmacokinetics·Antoine PetitcollinDavid Ternant
Mar 30, 2017·Clinical Pharmacokinetics·Niels Vande CasteeleWilliam J Sandborn
May 29, 2018·Clinical Pharmacokinetics·David TernantGilles Paintaud
Sep 27, 2018·Inflammatory Bowel Diseases·Reena Khanna, Niels Vande Casteele
Jul 14, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Pavine L C LefevreNiels Vande Casteele
Jun 10, 2020·JGH Open : an Open Access Journal of Gastroenterology and Hepatology·Isaac RodinKevan Jacobson

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Methods Mentioned

BETA
ELISA

Software Mentioned

Perl
NONMEM

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