代谢性骨病的药物代谢动力学和系统药理学。
Pharmacometrics and systems pharmacology for metabolic bone diseases.
机构信息
Metrum Research Group LLC, Tariffville, CT, USA.
Departments of Pathology & Cell Biology and Medicine, Columbia University Medical Center, New York, NY, USA.
出版信息
Br J Clin Pharmacol. 2019 Jun;85(6):1136-1146. doi: 10.1111/bcp.13881. Epub 2019 Feb 28.
Mathematical modelling and simulation (M&S) of drug concentrations, pharmacologic effects and the (patho)physiologic systems within which they interact can be powerful tools for the preclinical, translational and clinical development of drugs. Indeed, the Prescription Drug User Fee Act (PDUFA VI), incorporated as part of the FDA Reauthorization Act of 2017 (FDARA), highlights the goal of advancing model-informed drug development (MIDD). MIDD can benefit development across many drug classes, including for metabolic bone diseases such as osteoporosis, cancer-related and numerous rare metabolic bone diseases; conditions characterized by significant morbidity and mortality. A drought looms in terms of the availability of new drugs to better treat these devastating diseases. This review provides an overview of several M&S approaches ranging from simple pharmacokinetic to integrated pharmacometric and systems pharmacology modelling. Examples are included to illustrate the use of these approaches during the development of several drugs for metabolic bone diseases such as bisphosphonates, denosumab, teriparatide and sclerostin inhibitors (romosozumab and blosozumab).
药物浓度、药效学以及它们相互作用的（病理）生理系统的数学建模和模拟（M&S），可以成为药物临床前、转化和临床开发的有力工具。事实上，《处方药用户收费法案》（PDUFA VI）作为 2017 年《FDA 再授权法案》（FDARA）的一部分，强调了推进基于模型的药物开发（MIDD）的目标。MIDD 可以使许多药物类别受益，包括代谢性骨疾病，如骨质疏松症、癌症相关和许多罕见的代谢性骨疾病；这些疾病具有较高的发病率和死亡率。对于更好地治疗这些破坏性疾病的新药，目前面临着供应短缺的困境。本综述概述了几种 M&S 方法，范围从简单的药代动力学到综合药代动力学和系统药理学建模。包括了一些例子来说明这些方法在几种代谢性骨疾病药物（如双膦酸盐、地舒单抗、特立帕肽和硬骨素抑制剂（罗莫佐单抗和布洛索单抗）的开发过程中的应用。
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