Pharmacokinetics and pharmacodynamics of multiple weekly subcutaneous efalizumab doses in patients with plaque psoriasis

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.