在体外口腔腔透性评估,使药物吸收的模拟
Pankaj Dwivedi1, Priyata Kalra2, Haiying Zhou2
1Department of Pharmaceutical and Administrative Sciences, University of Health Sciences and Pharmacy in Saint Louis, St. Louis, MO 63110, USA.
Pharmaceutics
|July 30, 2025
概括
这项研究使用体外模型量化了通过口腔组织的药物透. 这些发现将有助于开发口服药物吸收的预测计算模型,加速通用产品的开发.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物运输 药物运输 药物运输
- 生物技术是生物技术.
背景情况:
- 口腔提供了一个方便的药物给药路线,绕过肝脏的第一通代谢.
- 在美国食品和药物管理局批准的口腔药物产品中,研究了精选的活性药物成分 (API).
研究的目的:
- 量化APIs在口腔药物中的粘膜透性质.
- 在药物吸收研究中评估人体衍生子语言 (HO-1-u-1) 和口腔 (EpiOralTM) 的体外组织模型.
主要方法:
- 通过使用propranolol和Lucifer Yellow作为标记物来评估表皮屏障特性.
- 人造唾液中APIs的脑外流量 (pH 6.7) 通过高性能液态染色学 (HPLC) 量化.
主要成果:
- 表面透系数 (Papp) 在API和组织模型之间有所不同.
- 口腔EpiOralTM模型显示出更大的区别,透值从3.31 ± 0.83 × 10−7厘米/秒 (阿西克洛维尔) 到2.56 ± 0.68 × 10−5厘米/秒 (苏夫坦尼尔).
- 在口腔EpiOralTM模型中观察到较高的组织相关剂量分数 (在sufentanil中高达8.5%).
结论:
- 来自体外模型的透数据将训练口服药物吸收的预测计算模型.
- 预计in silico建模策略将加速通用口腔产品的开发.
- 模型整合的证据将支持对仿制药开发的监管决策.
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