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

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


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Body Surface Area
  • Body Weight
  • C-Reactive Protein / analysis
  • Certolizumab Pegol / immunology
  • Certolizumab Pegol / pharmacokinetics*
  • Crohn Disease / blood
  • Crohn Disease / immunology
  • Crohn Disease / metabolism*
  • Female
  • Humans
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / pharmacokinetics*
  • Male
  • Middle Aged
  • Models, Biological*
  • Young Adult


  • Immunosuppressive Agents
  • C-Reactive Protein
  • Certolizumab Pegol