Population Pharmacokinetics of Efalizumab (Humanized Monoclonal Anti-CD11a Antibody) Following Long-Term Subcutaneous Weekly Dosing in Psoriasis Subjects

• Published in: Journal of clinical pharmacology 2005-04, Vol.45 (4), p.468-476
• Main Authors: Sun, Yu-Nien, Lu, Jian-Feng, Joshi, Amita, Compton, Peter, Kwon, Paul, Bruno, Rene A.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Analysis; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; CD11 Antigens - immunology; Dosage and administration; Drug Administration Schedule; Drug therapy; Efalizumab; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; nonlinear mixed effect modeling; NONMEM analysis; Pharmacokinetics; population pharmacokinetics; Psoriasis; Psoriasis - blood; Psoriasis - drug therapy; Psoriasis Area and Severity Index (PASI) score; Time
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270004272731

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.