Joshi Amita, Bauer Robert, Kuebler Peter, White Mark, Leddy Cecelia, Compton Peter, Garovoy Marvin, Kwon Paul, Walicke Patricia, Dedrick Russell
Department of Pharmacokinetic and Pharmacodynamic Sciences, MS 70, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
J Clin Pharmacol. 2006 Jan;46(1):10-20. doi: 10.1177/0091270005283282.
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.
依法利珠单抗是一种重组人源化单克隆IgG(1)抗体，已证明对治疗中度至重度慢性斑块状银屑病有效。依法利珠单抗是一种T细胞相互作用的靶向抑制剂，它与淋巴细胞功能相关抗原1（LFA-1）的CD11a亚基结合，从而阻止LFA-1与细胞间黏附分子1（ICAM-1）结合。作者回顾了依法利珠单抗临床开发项目的药代动力学和药效学数据，并讨论了这些数据如何导致选择成人最佳的每周皮下（SC）注射剂量（1.0mg/kg）的依法利珠单抗。每周1.0mg/kg或更高剂量的依法利珠单抗皮下注射对T淋巴细胞上CD11a的表达和可用的CD11a结合位点发挥了最大的药效学作用。每周皮下注射剂量大于1.0mg/kg并没有带来额外的益处；此外，更高的剂量并没有改变安全性。在依法利珠单抗的长期给药过程中，血清水平通常保持稳定，药效学标志物仍然受到最大程度的影响。
