角膜透性和25种药物的摄入:物种比较和定量结构-透性关系
Cleildo P Santana1,2, Brock A Matter1, Madhoosudan A Patil1
1Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Pharmaceutics
|June 28, 2023
概括
这项研究开发了定量结构-透性关系 (QSPRs),以预测,猪和牛种的角膜药物透性和吸收. 物理化学性质和组织厚度准确地解释了药物输送差异.
科学领域:
- 药理学 药理学是指药理学的学科.
- 眼部药物输送 眼部药物输送
- 生物医学工程 生物医学工程
背景情况:
- 角膜药物透性和吸收对于有效的眼部药物输送至关重要.
- 角膜特性中的特定物种差异可能会影响药物吸收.
- 定量结构-透性关系 (QSPRs) 为了解药物行为提供了一种预测方法.
研究的目的:
- 为了确定子,猪和牛角膜中25种药物的角膜透性和吸收.
- 建立定量结构-透性关系 (QSPRs),将药物特性与角膜透联系起来.
- 开发用于不同物种的眼部药物输送的预测模型.
主要方法:
- 使用微剂量药物的N-in-1 (磁带) 方法.
- 使用LC-MS/MS监测角膜药物透性和组织吸收.
- 使用多重线性回归 (MLR) 和Y随机化构建和验证了超过46,000个QSPR模型.
主要成果:
- 药物透性在子角膜中最高,牛和猪的角膜显示了相似的结果.
- 两种物种之间的透性差异部分归因于角膜厚度的变化.
- 在所有物种的透性和牛和猪角膜之间的吸收方面发现了很高的相关性 (R2 ≥0.94).
- 作为关键预测因素,MLR模型确定了脂友性 (LogD),异原子比 (HR),比 (NR),键接受器 (HBA),可旋键 (RB),折射指数 (IR) 和组织厚度 (TT).
结论:
- 一个单一的MLR方程有效地预测了子,猪和牛种的角膜药物透性和吸收.
- 整合药物的物理化学特性和角膜厚度的QSPR为优化眼部药物输送提供了强大的框架.
- 这些发现有助于预测角膜中的药物行为,有助于开发新的眼科配方.
相关概念视频
01:30Factors Affecting Drug Distribution: Tissue Permeability
247
The drug distribution process within the human body is a complex interplay of various physicochemical properties inherent to the drugs. These properties, including molecular size, ionization degree, partition coefficient, and stereochemical nature, significantly impact how drugs permeate biological membranes to reach their target tissues.
Small molecules with a molecular weight below 500 to 600 Daltons can easily pass through the capillary membrane, gaining access to different tissues. Larger...
Small molecules with a molecular weight below 500 to 600 Daltons can easily pass through the capillary membrane, gaining access to different tissues. Larger...
247
01:17Pore Transport and Ion-Pair Transport
522
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
522
01:24Cellular Membranes and Drug Transport
683
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
683
01:16Methods for Studying Drug Absorption: In vitro
262
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
262
01:25Physiological Barriers
3.6K
Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
3.6K
01:14Hepatic Drug Clearance: Role of Transporters
87
In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
87