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 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.
Mortensen
Deborah L
DL
Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080-4990, USA.
Walicke
Patricia A
PA
Wang
Xiaolin
X
Kwon
Paul
P
Kuebler
Peter
P
Gottlieb
Alice B
AB
Krueger
James G
JG
Leonardi
Craig
C
Miller
Bruce
B
Joshi
Amita
A
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen; C472181:efalizumab