title: Pharmacokinetics and pharmacodynamics of multiple weekly subcutaneous efalizumab doses in patients with plaque psoriasis.
abstract: 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 microg/mL, occurring approximately 2 days after a SC dose. Serum trough levels were 9 and 24 microg/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 approximately 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 approximately 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.
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080-4990, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Mortensen
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Walicke
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.forename: Paul
authors.initials: P
authors.lastname: Kwon
authors.forename: Peter
authors.initials: P
authors.lastname: Kuebler
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Craig
authors.initials: C
authors.lastname: Leonardi
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.forename: Amita
authors.initials: A
authors.lastname: Joshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000937:Antigen-Antibody Reactions; D040881:CD11a Antigen / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen; C472181:efalizumab