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Population Pharmacokinetics of Efalizumab (Humanized Monoclonal Anti‐CD11a Antibody) Following Long‐Term Subcutaneous Weekly Dosing in Psoriasis Subjects
Author(s) -
Sun YuNien,
Lu JianFeng,
Joshi Amita,
Compton Peter,
Kwon Paul,
Bruno Rene A.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004272731
Subject(s) - efalizumab , pharmacokinetics , medicine , dosing , psoriasis , population , psoriasis area and severity index , pharmacology , gastroenterology , immunology , plaque psoriasis , environmental health
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.