Rehlaender B N, Cho M J
Division of Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, 27599-7360, USA.
Pharm Res. 1998 Nov;15(11):1652-6. doi: 10.1023/a:1011936007457.
Pre-existing antibodies against a drug substance can significantly alter the pharmacokinetic profile of the drug in the circulation. Rapid clearance, mediated by complement or Fc receptors, occurs for crosslinked immune complexes, but not for complexes containing only one or two antibodies. With antibodies functioning as carrier proteins, monovalent antigens may enjoy a prolonged circulatory half-life, as observed in the case of digoxin, insulin, and various interleukins. While such an effect should be highly sensitive to fluctuations in antibody affinity and titer, it may present a means of extending the circulation of potent but rapidly cleared therapeutic agents. This mini-review attempts to delineate the causal relation between the factors influencing antibody binding and the circulatory life of a therapeutic agent, be it a small drug or a macromolecule.
针对药物的预先存在的抗体会显著改变药物在循环系统中的药代动力学特征。由补体或Fc受体介导的交联免疫复合物会迅速清除，但仅含一两个抗体的复合物则不会。由于抗体起着载体蛋白的作用，单价抗原可能具有延长的循环半衰期，地高辛、胰岛素及多种白细胞介素的情况就是如此。虽然这种效应应高度敏感于抗体亲和力和效价的波动，但它可能提供了一种延长强效但迅速清除的治疗药物循环时间的方法。本综述试图阐明影响抗体结合的因素与治疗药物（无论是小分子药物还是大分子药物）循环寿命之间的因果关系。
