Marsousi Niloufar, Desmeules Jules A, Rudaz Serge, Daali Youssef
Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland; Swiss Center for Applied Human Toxicology (SCAHT), Basel, Switzerland.
J Pharm Sci. 2017 Sep;106(9):2380-2391. doi: 10.1016/j.xphs.2017.04.035. Epub 2017 Apr 26.
Personalized medicine aims to determine the most adequate treatment and dose regimen to obtain the maximum efficacy and minimum side effect by taking into account patients' characteristics. For numerous reasons, one being ethical and methodological hurdles in including specific populations in clinical trials, innovative methods for optimization of drugs safety and efficacy in such patients have received increasing interest recently. Physiological-based pharmacokinetic (PBPK) modeling has emerged as a promising approach in designing adequate clinical trials and quantifying anticipated changes in unknown clinical situations. In this review, current state of knowledge on the usefulness of PBPK modeling in estimation of drug exposure in specific medical conditions including pregnancy, pediatrics, elderly, patients with liver or renal impairment, obesity, and following bariatric surgery were outlined. Modulations of key system parameters occurring in these patient populations were illustrated. Furthermore, the application of PBPK approach in dose recommendations and quantification of drug exposure in carriers of genetic polymorphisms was summarized. Despite the uncertainties and knowledge gaps related to parameters influencing drugs bioavailability in each clinical condition, PBPK models provide a valuable support for prospective dose recommendations and efficacy/safety assessment in special populations when consistent clinical data are lacking.
个性化医疗旨在通过考虑患者的特征来确定最适当的治疗方法和剂量方案，以获得最大疗效和最小副作用。由于多种原因，其中之一是将特定人群纳入临床试验存在伦理和方法上的障碍，因此，最近用于优化此类患者药物安全性和疗效的创新方法受到了越来越多的关注。基于生理的药代动力学（PBPK）模型已成为设计适当临床试验和量化未知临床情况下预期变化的一种有前途的方法。在这篇综述中，概述了PBPK模型在估计包括妊娠、儿科、老年、肝或肾功能损害患者、肥胖症患者以及减肥手术后患者等特定医疗状况下药物暴露方面的有用性的当前知识状态。阐述了这些患者群体中关键系统参数的调节情况。此外，总结了PBPK方法在基因多态性携带者的剂量推荐和药物暴露量化中的应用。尽管在每种临床情况下影响药物生物利用度的参数存在不确定性和知识空白，但当缺乏一致的临床数据时，PBPK模型为特殊人群的前瞻性剂量推荐和疗效/安全性评估提供了有价值的支持。
