Physicochemical characteristics and gastrointestinal absorption behaviors of S-propargyl-cysteine, a potential new drug candidate for cardiovascular protection and antitumor treatment. (6th November 2014)

• Record Type: Journal Article
• Authors: Ma, Guo; Zhang, Lin; Zhang, Peng; Bao, Xingfei; Zhou, Ning; Shi, Qingling; Zheng, Yuanting; Liu, Hongrui; Bu, Fengjiao; Zhang, Ying; Huang, Wenjie; Wang, Fen; Zhu, Yizhun; Cai, Weimin
• Is Part Of: Xenobiotica. Volume 45:Number 4(2015:Apr.)
• Page Start: 322
• Page End: 334
• Publication Date: 2014-11-06
• Subjects: Biopharmaceutics classification system -- dissociation constant -- equilibrium solubility -- gastrointestinal absorption -- partition coefficient -- physicochemical characteristics -- rat in situ perfusion -- S-propargyl-cysteine; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2014.980369
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 1. As a potential new drug candidate for cardiovascular protection and antitumor treatment, the physicochemical properties, gastrointestinal (GI) absorption behaviors and mechanisms of S -propargyl-cysteine (SPRC) were investigated in this study. 2. SPRC exhibited favorable solubility in aqueous media. The log P and log D values were low (≤1.93 ± 0.08). The p K a in the acidic and basic regions was 2.08 ± 0.02 and 8.72 ± 0.03, respectively. The isoelectric point was 5.40 ± 0.02. SPRC was stable in the rat GI fluids, and showed no obvious adsorption and metabolism in the rat GI tract. 3. SPRC displayed poor gastric absorption and favorable intestinal absorption in the rat in situ GI perfusion model. Absorption rate constants ( k a ), hourly absorption percentage ( P ) and apparent permeability coefficient ( P app ) of SPRC in the small intestine were ≥0.77 ± 0.06 h −1, 59.25 ± 4.02% and (7.99 ± 0.88) × 10 −5 cm/s, respectively. Absorption of SPRC exhibited a certain dependence on physiological pH and absorption region. Absorption of SPRC was not inhibited byl -methionine and 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid. 4. SPRC showed favorable oral absorption. It can be categorized as a BCS class I drug. The membrane pore transport appeared to be one of the predominant absorption modes for SPRC.