title: An overview of the pharmacokinetics and pharmacodynamics of efalizumab: a monoclonal antibody approved for use in psoriasis.
abstract: Efalizumab is a recombinant humanized monoclonal IgG(1) antibody shown to be efficacious for the treatment of moderate to severe chronic plaque psoriasis. Efalizumab, a targeted inhibitor of T cell interactions, binds to the CD11a subunit of lymphocyte function-associated antigen 1 (LFA-1), thereby preventing LFA-1 binding to intercellular adhesion molecule 1 (ICAM-1). The authors review the pharmacokinetic and pharmacodynamic data from the efalizumab clinical development program and discuss how these data led to selection of the optimal weekly subcutaneous (SC) dose of efalizumab (1.0 mg/kg) in adults. Efalizumab SC dosages of 1.0 mg/kg/wk or greater exerted maximal pharmacodynamic effects for CD11a expression and available CD11a binding sites on T lymphocytes. Dosages greater than 1.0 mg/kg/wk SC did not provide additional benefits; moreover, higher doses did not alter the safety profile. During long-term administration of efalizumab, serum levels were generally stable and pharmacodynamic markers remained maximally affected.
authors.affiliation: Department of Pharmacokinetic and Pharmacodynamic Sciences, MS 70, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Amita
authors.initials: A
authors.lastname: Joshi
authors.forename: Robert
authors.initials: R
authors.lastname: Bauer
authors.forename: Peter
authors.initials: P
authors.lastname: Kuebler
authors.forename: Mark
authors.initials: M
authors.lastname: White
authors.forename: Cecelia
authors.initials: C
authors.lastname: Leddy
authors.forename: Peter
authors.initials: P
authors.lastname: Compton
authors.forename: Marvin
authors.initials: M
authors.lastname: Garovoy
authors.forename: Paul
authors.initials: P
authors.lastname: Kwon
authors.forename: Patricia
authors.initials: P
authors.lastname: Walicke
authors.forename: Russell
authors.initials: R
authors.lastname: Dedrick
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens / Q000276:immunology*; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; C472181:efalizumab