炎症性肠病生物制剂群体药动学研究进展

Research Progress in Population Pharmacokinetics of Biologics in Inflammatory Bowel Disease

关键词:  炎症性肠病  生物制剂  群体药动学  研究进展  个体化治疗

Key words:  inflammatory bowel disease  biologics  population pharmacokinetics  research progress  individualized therapy

摘要:

目的：炎症性肠病（inflammatory bowel diseases, IBD）是一种慢性、非特异性肠道炎症性疾病。近年来，生物制剂已成为IBD的重要治疗手段，显著改善了患者的临床预后。然而，生物制剂在临床应用中也面临着诸多挑战，其药动学和药效学存在显著的个体差异。随着IBD生物制剂群体药动学（population pharmacokinetics, PPK）研究的不断增加，研究者们逐渐揭示了生物制剂的PPK特征以及影响其清除率的诸多因素。本文旨在综述PPK研究进展，对生物制剂的药动学特征进行全面而深入的描述，为生物制剂在IBD治疗中的个体化用药提供坚实的理论依据。方法：通过检索PubMed，EMBASE和Web of Science三大权威数据库，对IBD生物制剂的PPK模型研究进行全面汇总和深入分析，重点介绍影响生物制剂清除率的关键因素和PPK模型，并进一步探讨了当前研究中存在的挑战以及未来的发展方向。结果: 最终纳入51篇生物制剂PPK模型研究文献，涵盖了目前临床常用的生物制剂，包括英夫利昔单抗29篇，阿达木单抗7篇，乌司奴单抗5篇，戈利木单抗4篇，维得利珠单抗3篇以及赛妥珠单抗3篇。分析结果显示，影响IBD患者生物制剂药动学的主要因素包括体重、血清白蛋白水平、C-反应蛋白水平以及抗药抗体的产生等。这些因素相互作用，共同决定了生物制剂在体内的分布、代谢和清除过程，进而影响治疗效果。结论: 生物制剂在IBD患者个体间存在显著的差异性。因此，在临床实践中，针对不同生物制剂、人群以及疾病类型，应充分结合药物的特性以及患者的疾病特点，制定精准的个性化给药方案，以最大限度提高治疗效果，减少不良反应。

Abstract:

Objective: Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition of the intestine. In recent years, biologics have become an important therapeutic option for IBD, significantly improving clinical outcomes for patients. However, the clinical use of biologics also faces many challenges, including significant inter-individual variability in pharmacokinetics and pharmacodynamics. With the increasing number of population pharmacokinetic (PPK) studies on IBD biologics, researchers have gradually elucidated the PPK characteristics of biologics and the factors influencing their clearance. This article aims to review the progress in PPK research, provide a comprehensive and in-depth description of the pharmacokinetic characteristics of biologics, and offer a solid theoretical basis for individualized dosing of biologics in IBD treatment. Methods: By searching the three authoritative databases PubMed, EMBASE, and Web of Science, we conducted a comprehensive summary and in-depth analysis of PPK model studies on IBD biologics, focusing on the key factors influencing the clearance of biologics and the PPK models, and further discussed the current challenges and future directions in research. Results: A total of 51 PPK model studies on biologics were included, covering commonly used biologics in clinical practice, including 29 studies on infliximab, 7 on adalimumab, 5 on ustekinumab, 4 on golimumab, 3 on vedolizumab, and 3 on certolizumab pegol. The analysis showed that the main factors affecting the pharmacokinetics of biologics in IBD patients include body weight, serum albumin levels, C-reactive protein levels, and the presence of antidrug antibodies. These factors interact with each other to determine the distribution, metabolism, and clearance of biologics in the body, thereby affecting therapeutic outcomes. Conclusion: There is significant inter-individual variability in the use of biologics among IBD patients. Therefore, in clinical practice, individualized dosing regimens should be developed by fully considering the characteristics of the drugs and the disease features of patients, tailored to different biologics, patient populations, and disease types, in order to maximize therapeutic efficacy and minimize adverse reactions.