Assessment strategies for drug permeability during drug discovery and development
10.16438/j.0513-4870.2021-0102
- VernacularTitle:药物通透性在新药发现和开发阶段的评估策略
- Author:
Wen-qian LI
;
Jing-jing HAN
;
Xian ZHANG
;
Run-ze XU
;
Jin YANG
- Publication Type:Research Article
- Keywords:
oral drug;
permeability;
parallel artificial membrane permeability assay;
Caco-2;
Ussing chamber;
effective permeability coefficient;
fraction absorbed
- From:
Acta Pharmaceutica Sinica
2021;56(5):1279-1285
- CountryChina
- Language:Chinese
-
Abstract:
Permeability is a key factor in the bioavailability of oral drugs. Therefore, in the early stage of drug discovery, accurate and efficient evaluation of drug permeability is essential. The parallel artificial membrane permeability assay (PAMPA) with Caco-2 cells model was used by the industry as early evaluation methods. At present, the Ussing chamber rat model is also widely used. This review summarizes the human data for the in vivo single-pass perfusion technique (Loc-I-Gut) – the gold standard, and then focuses on the basic principles, experimental operation, and efficiency of the three in vitro methods, with correlation to the effective permeability coefficient (Peff) and fractional absorbed (Fa) in man. We provide recommendations for the use of proper permeability methods at different stages in drug discovery and development.
