我从大学毕业的那一年是一个老家庭朋友退休的同年。他花了大多数职业生涯设计和部署在美国的农场设备。当我要求建议时，当我进入劳动力时，他告诉我一个故事。
Three months into retirement, a company in California asked him to fly out and consult with their mechanics on why a piece of equipment wasn’t working. He flew out, spent 5 minutes at the company’s site, drew an “X” in chalk on the equipment, and flew home. They called the next day and asked what they needed to do. He directed them to the “X”. As simple as an “X” is, it represented years of experience and understanding of the intricacies of the machine and what could potentially go wrong.
他说这个故事的寓意是，“很高兴知道把X的地方”。
当然这可以在工程，制造或建筑领域工作（仅限几个），但这将如何适用于我们正在处理复杂的生活物种，这些物种在其遗传妆容中大大不同？关于我们测试的药物的适应症，模态和药理学的差异如何？
So where to put the “X” in pharmaceutical development? That’s what we in PK/PD modeling and simulation strive to address. We offer a multitude of different services. These range from noncompartmental analysis to help parameterize and guide the interpretation of pharmacokinetic, pharmacodynamic, or toxicology studies, to fully mechanistic PK/PD models taking into account the anatomical physiology of test species, the physiochemical properties of the drug, and the metabolic profile tested in vitro. These mechanistic models mathematically describe the PK and simulate a range of outcomes to help design better studies and make better decisions.
Covance works with different partners from academia to large pharma and everywhere in between. We work across all phases of development and across a myriad of molecule types, disease states and routes of administration.
Over the next six months we will be introducing topics that we get regular questions about from across the industry and discuss how we help to offer up modeling and simulation solutions to progress their programs more efficiently.
以下是我们计划覆盖的一些主题：
Target Mediated Drug Disposition (TMDD) for Biologics
TMDD是在开发生物学时观察到的非常常见的现象。药物的药代动力学性质受到药理学靶标的高亲和力的影响。虽然在许多情况下对目标的这种亲和力是对药理学的优势，药物的影响，我们将利用TMDD PK模型来优化治疗窗，给药方案，另外，从临床前物种到临床的翻译。yaboapp体育官网
非组分分析：考虑因素，效率和发送
In the past year, the Covance modeling and simulation team has had the opportunity to support more than 170 unique clients. We see a wide variety of approaches and opinions from handling of anomalous data, to appropriate sampling schemes and parameters to characterize the PK/PD. In this post we will discuss our approach which has been informed by observation and consensus across the industry, the potential pitfalls that are often missed in Noncompartmental analysis, and how to effectively bring forward the data into SEND ready domains.
Physiologically Based PK Models for Understanding and Predicting DDI’s
With the recent updates to the FDA guidances on drug-drug interactions (DDI) there is a buzz in the industry around utilizing risk-based approaches in assessing potential DDI and further mitigating potential DDIs as we design clinical trials and develop product labeling. We will discuss the utilization of the in vitro metabolism and drug transporter data to build mechanistic models that can be utilized to simulate potential DDI with a range of perpetrator drugs.
First in Human Dose Predictions: Making Applicable to Your Drug
非线性药物动力学,vitro-in vivo。柯尔elations, narrow safety margins, non-translational systemic exposure, drug transporters, applicable preclinical species, target engagement, body surface area scaling and allometry, MABEL, mechanistic interspecies scaling (the list goes on)…
我们肯定可以同意有许多因素，以了解您的临床前数据，并证明安全的第一人体剂量。yaboapp体育官网让我们试着简化这种方法。在这篇文章中，我们将讨论我们如何评估赞助计划，帮助了解局限性，并迎合一种方法，因此我们可以置信和设计一个捕获所有终点的阶段。
基于模型的药物开发：预测，定义，精炼
There is an old adage that “All models are wrong, but some are useful”. Our goal is to improve this statement. We feel that all models have limitations, but we want to do three things to ensure the majority are useful:
- 考虑模型可能有用的位置，并且模型在毒品的整体发展范围内意味着什么
- Understand the limitations and specific client perspectives, so we can interpret appropriately
- Improve each iteration as we acquire additional information (knowledge and data)
这篇文章将讨论我们的方法，我们认为我们可以帮助找到节省时间，资源和金钱的解决方案。
Population PK/PD Analysis and Understanding Covariates
人口药代动力学和药效学分析用于帮助了解靶人群中的差异和变异，以帮助测定安全和有效的药物管理。它们用于支持临床前和临床数据，并允许集成稀疏数据，但也可以用于稀yaboapp体育官网疏和密集数据的组合。We will share our experiences using these techniques across the phases of drug development to help investigate the sources of variability (e.g., bodyweight, metabolic functions, patient demographics, etc) and how to adjust the dosing regimens based on the covariates that impact dose-concentration-efficacy/safety relationships.
