Polybasic research on the biopharmaceutical characteristics of 20 (S)-protopanaxadiol.
- Author:
Xin JIN
1
;
Zhen-Hai ZHANG
;
E SUN
;
Xiao-Bin TAN
;
Hai-Jian XIA
;
Qi-Yuan LIU
;
Xiao-Bin JIA
Author Information
1. Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China.
- Publication Type:Journal Article
- MeSH:
Administration, Oral;
Animals;
Area Under Curve;
Biological Availability;
Caco-2 Cells;
Humans;
Intestinal Absorption;
Male;
Permeability;
Rats;
Rats, Sprague-Dawley;
Sapogenins;
administration & dosage;
blood;
chemistry;
metabolism;
pharmacokinetics;
Solubility;
Tissue Distribution
- From:
Acta Pharmaceutica Sinica
2013;48(3):411-416
- CountryChina
- Language:Chinese
-
Abstract:
In this study, the biopharmaceutical properties of 20 (S)-protopanaxadiol (PPD) were studied. Firstly, the equilibrium solubility and apparent oil/water partition coefficient of PPD were used to predict the absorption in vivo. Meanwhile the membrane permeability and absorption window were studied by Caco-2 cell model and single-pass intestinal perfusion model. Furthermore, the bioavailability and metabolism were combined to study the absorption properties and metabolic properties in vivo. All of them were used to provide theoretical and practical foundation for designing PPD preparation. The results showed that PPD is poorly water-soluble, and the equilibrium solubility in water is only 35.24 mg x L(-1). The oil-water partition coefficient is 46.21 (logP = 1.66). By Caco-2 cell model, the results showed PPD uptake in general, and it also has efflux. By in situ intestinal perfusion model, the results showed that the absorption of PPD in the intestine is good, and the effective permeability coefficient were duodenum > jejunum > ileum > colon. The oral bioavailability of PPD was 29.39%. It was not well. Metabolic studies showed PPD in vivo presented a wide spread metabolism. So the main factors that restricted oral bioavailability of PPD were the poor solubility and first-pass effect.
