在PBPK平台中探索IVIVC解卷方法:以托法西提尼布为案例
1Drug Product Design & Supply (DPDS), Global Biopharmaceutics, Pfizer Zaventem, Hermeslaan 11, 1932, Zaventem, Belgium. Bart.hens@pfizer.com.
The AAPS journal
|January 6, 2026
概括
这项研究验证了用于修改释放药物开发的解方法. 这些模型将体外溶解与体外吸收联系起来,帮助配方和监管过程.
科学领域:
- 药理动力学和药物输送方法
- 制药科学 制药科学
- 生物制药生物制药公司
背景情况:
- 修改释放 (MR) 药物产品需要了解体外-体内相关性,以获得一致的性能.
- 在体外-体内相关性 (IVIVC) 对于优化MR配方和支持监管决策至关重要.
- 托法西提尼布被用作一种模型化合物来评估解卷方法.
研究的目的:
- 评估GPXTM内IVIVC的三种解卷方法 (数值,分区,机械).
- 评估这些模型从体外溶解数据中预测体内药物吸收的能力.
- 在生理学基础的药理动力学 (PBPK) 框架中证明基于解卷的IVIVC的实用性.
主要方法:
- 开发了多法西提尼布的原型MR配方,释放速度不同.
- 在健康志愿者中进行了一项随机交叉研究,以获得血度-时间数据.
- 应用了数值,区间和机械解卷方法来得出体内分数吸收的概况.
- 使用卷曲数据模拟了血度-时间概况,并将其与观察到的临床数据进行了比较.
- 计算了药物动力学参数 (Cmax,AUC) 的预测误差和置信区间,以评估生物等价性.
主要成果:
- 解卷方法成功地导出了体内微分被吸收的概况.
- 模拟的血形状与观察到的临床数据有很好的一致性.
- 对Cmax和AUC的预测错误在可接受的范围内,这表明生物等价性评估是成功的.
- 这项研究表明了在PBPK框架内基于解卷的IVIVC的实用性.
结论:
- 基于解密的IVIVC模型是修改释放药物产品开发的宝贵工具.
- 这些模型有助于优化配方,并支持监管灵活性.
- 该方法为管理配方生命周期和评估溶解变异性提供了一个强大的策略.
关键词:
在体外-体内相对应的相关性.IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVCPBPKK PBPK 的意思是什么意思解体解体是一种解体.建模 建模模型 建模模型模拟模拟是指一个模拟模拟.托法西提尼布 (tofacitinib) 是一种更多相关视频
08:36Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
1.5K
06:14Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients
Published on: October 15, 2017
8.7K
相关概念视频
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
314
Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
314
01:12Analysis of Population Pharmacokinetic Data
671
Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
671
01:28Biopharmaceutics and Pharmacokinetics: Overview
3.3K
Understanding drugs, drug products, and their performance in pharmaceutical science is pivotal. Drugs, whether simple molecules or complex compounds, are designed to interact with the body's biological systems to diagnose, treat, or prevent diseases. Drug products include various delivery systems such as tablets, capsules, injections, and inhalers. The performance of these drug products is gauged by their ability to deliver the active ingredient to the desired site of action at the...
3.3K
01:20Measurement of Bioavailability: Pharmacodynamic Methods
228
Pharmacodynamic methods provide insights into a drug's effects on physiological processes over time and play a crucial role in understanding bioavailability and therapeutic efficacy. These methods can be broadly classified into acute pharmacological and therapeutic response approaches, each with distinct mechanisms and applications.The acute pharmacological response method directly correlates a drug's physiological effects, such as ECG or pupil diameter changes, to its time course in the body.
228
00:54Noncompartmental Analysis: Miscellaneous Pharmacokinetic Parameters
422
The noncompartmental approach is a widely used method in pharmacokinetics to assess drugs' behaviors in the body. It considers several factors, including clearance, bioavailability, and total volume of distribution.
One key aspect of the noncompartmental approach is determining a drug's total clearance. This can be done by dividing the drug dose by the area under the concentration-time curve from zero to infinity. The area under the concentration-time curve represents the drug's...
One key aspect of the noncompartmental approach is determining a drug's total clearance. This can be done by dividing the drug dose by the area under the concentration-time curve from zero to infinity. The area under the concentration-time curve represents the drug's...
422
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
480
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
480