Population pharmacokinetics of efalizumab (humanized monoclonal anti-CD11a antibody) following long-term subcutaneous weekly dosing in psoriasis subjects.
The population pharmacokinetics of efalizumab was characterized in patients with moderate to severe plaque psoriasis. The study included 1088 subjects who received 1 or 2 mg/kg/wk subcutaneous efalizumab for 12 weeks from a phase I (64 subjects) and 3 phase III studies with day 42 and/or day 84 trough levels (1024 patients). Due to the limitation of the data, a 1-compartment model with first-order absorption and elimination was used to fit the data. The population means for V/F, Ka, and CL/F were 9.13 L, 0.191 day(-1), and 1.29 L/d, respectively, for a typical subject receiving a 1-mg/kg dose. Interindividual variability in CL/F was 48.2%. Body weight has the largest influence on CL/F. Other covariates (obesity, baseline lymphocyte counts, Psoriasis Area and Severity Index score, and age) had only modest effects. Subjects in the 2-mg/kg dose group had a 24.0% lower CL/F, consistent with nonlinear pharmacokinetics of efalizumab. The results of this analysis support the current body weight-adjusted dosing strategy.
Sun
Yu-Nien
YN
Late Stage BioTherapeutics, Department of Pharmacokinetic and Pharmacodynamic Sciences, MS 70, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
Lu
Jian-Feng
JF
Joshi
Amita
A
Compton
Peter
P
Kwon
Paul
P
Bruno
Rene A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens / Q000276:immunology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood* / Q000188:drug therapy*; D013995:Time
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; C472181:efalizumab