Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease.
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.
SGS Exprimo NV, Generaal de Wittelaan 19A Bus 5, Mechelen, Belgium.
Janet R
JR
Wade
UCB Ltd, Slough, Berkshire, England.
Gerry
G
Parker
UCB, Research Triangle Park, NC, USA.
Gordana
G
Kosutic
The University of Western Ontario, London, Ontario, Canada.
Brian G
BG
Feagen
Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
William J
WJ
Sandborn
SGS Exprimo NV, Generaal de Wittelaan 19A Bus 5, Mechelen, Belgium.
Christian
C
Laveille
UCB Ltd, Slough, Berkshire, England.
Ruth
R
Oliver
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D001830:Body Surface Area; D001835:Body Weight; D002097:C-Reactive Protein / Q000032:analysis; D000068582:Certolizumab Pegol / Q000276:immunology / Q000493:pharmacokinetics*; D003424:Crohn Disease / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D055815:Young Adult
D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D000068582:Certolizumab Pegol
Crohn's disease; NONMEM; anti-TNF; certolizumab pegol; covariates