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- Title
Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease.
- Authors
Wade, Janet R.; Parker, Gerry; Kosutic, Gordana; Feagen, Brian G.; Sandborn, William J.; Laveille, Christian; Oliver, Ruth
- 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.
- Subjects
BIOMARKERS; CONFIDENCE intervals; CREATININE; CROHN'S disease; IMMUNOADSORPTION; MONOCLONAL antibodies; PHARMACOKINETICS; RACE; RESEARCH funding; SERUM albumin; TUMOR necrosis factors; CAUSAL models; BODY mass index; TREATMENT effectiveness; ABSORPTION; DATA analysis software; CHEMICAL inhibitors
- Publication
Journal of Clinical Pharmacology, 2015, Vol 55, Issue 8, p866
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1002/jcph.491