生物模拟分散固相微提取:一种用于高通量估计人类口服吸收有机化合物的新概念
Maria Pau García-Moll1, Llucia García-Moll1, Enrique Javier Carrasco-Correa2
1FI-TRACE Group, Department of Chemistry, University of the Balearic Islands, Carretera de Valldemossa, km 7.5, Palma de Mallorca E-07122, Spain.
Analytical chemistry
|August 24, 2023
概括
一种新的体外试验方法使用生物模拟微提取方法与固定脂质来预测人类口服吸收和有机化合物的肠道透性,避免动物试验. 这为环境污染物和药品提供了更快的选工具.
科学领域:
- 环境化学环境化学
- 分析化学 分析化学
- 毒理学 毒理学 毒理学
背景情况:
- 预测人类口服吸收的传统方法通常依赖于动物模型和像log P这样的参数,这些参数不能完全捕捉复杂的生物相互作用.
- 需要验证的体外分析方法来准确预测有机化合物的口服吸收和生物积累,包括药品和环境污染物.
研究的目的:
- 开发和验证一种新的生物模拟微提取方法,用于估计药品和环境污染物的有效肠道透性.
- 建立一个可靠的体外方法来预测口服吸收,而不需要动物模型.
主要方法:
- 一种生物模拟微提取技术,利用在有机聚合物吸附相上固定化脂胆作为血替代物.
- 在吸附相上探索脂质结构结构 (单层,双层,纳米纤维) 的探索.
- 使用生物模拟提取数据,Log D和芳香环数量,开发人类内皮膜透性的预测模型.
主要成果:
- 仅仅生物仿真提取数据就为预测人类内透度提供了良好的相关性 (R2 = 0.76).
- 将日志D和芳香环数纳入多重线性回归模型显著提高了预测准确性 (R2 = 0.88).
- 开发的方法表明,与传统的分子描述符相比,它具有潜力作为一个优越的参数,用于透性预测.
结论:
- 这种新的生物模拟微提取方法提供了一种经过验证的体外方法,用于预测人类口服吸收和肠道透性.
- 该方法为快速选有机污染物和制药提供了宝贵的工具,有助于人类暴露和环境风险评估.
- 该研究为开发更快,无动物查方法的化学安全和暴露评估开辟了新的途径.
相关概念视频
01:09Methods for Studying Drug Absorption: In situ
264
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
264
01:16Methods for Studying Drug Absorption: In vitro
256
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...
256
01:15Non-Oral Extravascular Drug Absorption Routes
239
Non-oral extravascular routes, which encompass sublingual, buccal, topical, intramuscular, and inhalation methods, primarily utilize passive diffusion to transport drugs into the systemic circulation. The absorption rates and effectiveness of these routes depend on the drug's physicochemical properties, as well as the patient's anatomical and pathophysiological state.
Lipophilic drugs that are stable at salivary pH (6) and exhibit minimal binding to the oral mucosa are absorbed more...
Lipophilic drugs that are stable at salivary pH (6) and exhibit minimal binding to the oral mucosa are absorbed more...
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