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Pharmacokinetics and Pharmacodynamics of Multiple Weekly Subcutaneous Efalizumab Doses in Patients With Plaque Psoriasis
Author(s) -
Mortensen Deborah L.,
Walicke Patricia A.,
Wang Xiaolin,
Kwon Paul,
Kuebler Peter,
Gottlieb Alice B.,
Krueger James G.,
Leonardi Craig,
Miller Bruce,
Joshi Amita
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004270260
Subject(s) - efalizumab , pharmacodynamics , pharmacokinetics , psoriasis , medicine , pharmacology , population , cd11a , bioequivalence , crossover study , psoriasis area and severity index , plaque psoriasis , placebo , immunology , pathology , receptor , integrin , environmental health , cd18 , alternative medicine
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.