Amgen Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, United States of America.
PLoS One. 2019 May 23;14(5):e0217061. doi: 10.1371/journal.pone.0217061. eCollection 2019.
In this study we compared the pharmacokinetic profile of four unrelated antibodies, which do not bind to mammalian antigens, in IgG1 and IgG2 frameworks in both rats and non-human primates (NHP). This allowed for extensive cross comparison of the impact of antibody isotype, complementarity determining regions (CDR) and model species on pharmacokinetics without the confounding influence of antigen binding in the hosts. While antibody isotype had no significant impact on the pharmacokinetics, the CDRs do alter the profile, and there is an inverse correlation between the neonatal Fc receptor (FcRn) affinity and pharmacokinetic performance. Faster clearance rates were also associated with higher isoelectric points; however, although this panel of antibodies all possess basic isoelectric points, ranging from 8.44 to 9.18, they also have exceptional in vivo half-lives, averaging 369 hours, and low clearance rates, averaging 0.18 ml/h/kg in NHPs. This pattern of pharmacokinetic characteristics was conserved between rats and NHPs.
在这项研究中，我们比较了四种不与哺乳动物抗原结合的非相关抗体在大鼠和非人灵长类动物（NHP）中的 IgG1 和 IgG2 框架中的药代动力学特征。这使得我们能够在不考虑宿主中抗原结合的干扰的情况下，广泛比较抗体同种型、互补决定区（CDR）和模型物种对药代动力学的影响。虽然抗体同种型对药代动力学没有显著影响，但 CDR 确实改变了图谱，并且新生儿 Fc 受体（FcRn）亲和力与药代动力学性能呈反比。更快的清除率也与更高的等电点相关；然而，尽管这组抗体都具有碱性等电点，范围从 8.44 到 9.18，但它们在体内也具有出色的半衰期，平均为 369 小时，清除率低，平均为 0.18ml/h/kg 在 NHP 中。这种药代动力学特征模式在大鼠和 NHP 之间是保守的。
