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: Deborah L Mortensen, Patricia A Walicke, Xiaolin Wang, Paul Kwon, Peter Kuebler, Alice B Gottlieb, James G Krueger, Craig Leonardi, Bruce Miller, Amita Joshi
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 45 Issue 3 Pg. 286-98 (Mar 2005) ISSN: 0091-2700 [Print] England
• PMID: 15703364 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CD11a Antigen
• efalizumab

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (immunology, pharmacokinetics, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antigen-Antibody Reactions
• CD11a Antigen (immunology)
• Down-Regulation
• Female
• Humans
• Leukocyte Count
• Male
• Middle Aged
• Psoriasis (blood, immunology, therapy)
• T-Lymphocytes (drug effects, immunology)