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Pharmacokinetics and Pharmacodynamics of Multiple Weekly Subcutaneous Efalizumab Doses in Patients With Plaque Psoriasis

From Genentech, Inc, South San Francisco, California (Ms Mortensen, Dr Walicke, Dr Wang, Dr Kwon, Dr Kuebler, Dr Joshi); UMDNJ–Robert Wood Johnson Medical School, New Brunswick, New Jersey (Dr Gottlieb); The Rockefeller University, New York (Dr Krueger); Central Dermatology, St. Louis, Missouri (Dr Leonardi); and Oregon Medical Research Center, Portland, Oregon (Dr Miller).

Efalizumab pharmacokinetics, pharmacodynamics, and efficacy were assessed after subcutaneous administration of 1.0 or 2.0 mg/kg/wk for 12 weeks with 12 weeks of follow-up in subjects with psoriasis. Steady-state serum concentrations were achieved by 4 and 8 weeks, respectively. C_max was 12 and 31 µg/mL, occurring 2 days after a SC dose. Serum trough levels were 9 and 24 µg/mL, and CL/F_ss was 24 and 16 mL/kg/d. At both doses, CD11a expression on T lymphocytes was maximally down-modulated to 20% of baseline, and CD11a binding sites were >95% saturated. The extent of this PD effect was less for other leukocytes. Leukocyte counts increased by 40%, with the majority of this increase related to a significant but reversible increase in the lymphocyte population. Maximal pharmacodynamic effects were sustained at both dose levels through the course of treatment and were commensurate with improvements in psoriasis.

Key Words: Efalizumab • pharmacokinetics • pharmacodynamics • psoriasis • anti-CD11a

Address for reprints: Amita Joshi, PhD, Pharmacokinetic and Pharmacodynamic Sciences (MS #70), Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080-4990.

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