Population pharmacokinetic modeling of ustekinumab, a human monoclonal antibody targeting IL-12/23p40, in patients with moderate to severe plaque psoriasis.
The population pharmacokinetics of ustekinumab are characterized in patients with moderate to severe plaque psoriasis in 2 Phase 3 studies (PHOENIX 1 and PHOENIX 2). Serum concentration data from 1937 patients are analyzed to determine pharmacokinetic characteristics of ustekinumab and to assess factors that may contribute to their variability. The population typical mean (percentage relative standard error) values for apparent clearance, apparent volume of distribution, and absorption rate constant from the final covariate model are 0.465 L.day(-1) (2.0%), 15.7 L (2.0%), and 0.354 day(-1) (16.2%), respectively. The interindividual variabilities for apparent clearance and apparent volume of distribution are 41.0% and 33.2%, respectively. Of the factors evaluated in this analysis, body weight, diabetes, and positive immune response (antibodies to ustekinumab) are important covariates affecting the apparent clearance and/or apparent volume of distribution of ustekinumab. To fully understand the clinical relevance of these results, the covariate findings need to be evaluated concurrently with the efficacy and safety data.
Zhu
Yaowei
Y
Pharmacokinetics, Modeling & Simulation, Clinical Pharmacology Sciences, Centocor Research & Development, Inc, 200 Great Valley Parkway, Malvern, PA 19355, USA.
Hu
Chuanpu
C
Lu
Ming
M
Liao
Sam
S
Marini
Joseph C
JC
Yohrling
Jennifer
J
Yeilding
Newman
N
Davis
Hugh M
HM
Zhou
Honghui
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001835:Body Weight; D017326:Clinical Trials, Phase III as Topic; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D014018:Tissue Distribution; D000069549:Ustekinumab; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D018664:Interleukin-12; D000069549:Ustekinumab