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

From the Department of Pharmacokinetic and Pharmacodynamic Sciences (Dr Sun, Dr Lu, Dr Joshi, Dr Bruno), Department of Specialty Biotherapeutics (Dr Kwon), and Biostatistics (Mr Compton), Genentech, Inc, South San Francisco, California.

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.

Key Words: Efalizumab • psoriasis • population pharmacokinetics • nonlinear mixed effect modeling • NONMEM analysis • Psoriasis Area and Severity Index (PASI) score

Address for reprints: Amita Joshi, PhD, Late Stage BioTherapeutics, Department of Pharmacokinetic and Pharmacodynamic Sciences, MS 70, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080.

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