Rodríguez-Fernández Karine, Mangas-Sanjuán Víctor, Merino-Sanjuán Matilde, Martorell-Calatayud Antonio, Mateu-Puchades Almudena, Climente-Martí Mónica, Gras-Colomer Elena
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain.
Interuniversity Research Institute for Molecular Recognition and Technological Development, Polytechnic University of Valencia, 46100 Valencia, Spain.
Pharmaceutics. 2022 Mar 16;14(3):654. doi: 10.3390/pharmaceutics14030654.
The treatment of psoriasis has been revolutionized by the emergence of biological therapies. Monoclonal antibodies (mAb) generally have complex pharmacokinetic (PK) properties with nonlinear distribution and elimination. In recent years, several population pharmacokinetic/pharmacodynamic (PK/PD) models capable of describing different types of mAb have been published. This study aims to summarize the findings of a literature search about population PK/PD modeling and therapeutic drug monitoring (TDM) of mAb in psoriasis. A total of 22 articles corresponding to population PK/PD models of tumor necrosis factor (TNF)-α inhibitors (adalimumab and golimumab), interleukin (IL)-23 inhibitors (guselkumab, tildrakizumab, and risankizumab), IL-23/IL-12 inhibitor (ustekinumab), and IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) were collected. A summary of the clinical trials conducted so far in psoriasis was included, together with the current structural population PK and PD models. The most significant and clinical covariates were body weight (BW) and the presence of immunogenicity on clearance (CL). The lack of consensus on PK/PD relationships has prevented establishing an adequate dosage and, therefore, accentuates the need for TDM in psoriasis.
生物疗法的出现彻底改变了银屑病的治疗方式。单克隆抗体(mAb)通常具有复杂的药代动力学(PK)特性,其分布和消除呈非线性。近年来,已经发表了几种能够描述不同类型mAb的群体药代动力学/药效学(PK/PD)模型。本研究旨在总结关于银屑病中mAb的群体PK/PD建模和治疗药物监测(TDM)的文献检索结果。共收集了22篇与肿瘤坏死因子(TNF)-α抑制剂(阿达木单抗和戈利木单抗)、白细胞介素(IL)-23抑制剂(古塞库单抗、替拉珠单抗和司库奇尤单抗)、IL-23/IL-12抑制剂(乌司奴单抗)以及IL-17抑制剂(司库奇尤单抗、依奇珠单抗和布罗达单抗)的群体PK/PD模型相关的文章。其中包括了迄今为止在银屑病中进行的临床试验总结,以及当前的结构群体PK和PD模型。最显著的临床协变量是体重(BW)和清除率(CL)上免疫原性的存在情况。PK/PD关系缺乏共识阻碍了确定合适的剂量,因此突出了银屑病中TDM的必要性。