Physicochemical characteristics and gastrointestinal absorption behaviors of S-propargyl-cysteine, a potential new drug candidate for cardiovascular protection and antitumor treatment.
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 pKa 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 (ka), hourly absorption percentage (P) and apparent permeability coefficient (Papp) 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 by l-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.
['Ma|Guo|G|', 'Zhang|Lin|L|', 'Zhang|Peng|P|', 'Bao|Xingfei|X|', 'Zhou|Ning|N|', 'Shi|Qingling|Q|', 'Zheng|Yuanting|Y|', 'Liu|Hongrui|H|', 'Bu|Fengjiao|F|', 'Zhang|Ying|Y|', 'Huang|Wenjie|W|', 'Wang|Fen|F|', 'Zhu|Yizhun|Y|', 'Cai|Weimin|W|']
D000818:Animals D000970:Antineoplastic Agents D002319:Cardiovascular System D055598:Chemical Phenomena D002851:Chromatography, High Pressure Liquid D003545:Cysteine D065569:Gastrointestinal Absorption D006863:Hydrogen-Ion Concentration D008297:Male D023421:Models, Animal D010539:Permeability D017207:Rats, Sprague-Dawley D012995:Solubility D053719:Tandem Mass Spectrometry
physicochemical characteristics gastrointestinal absorption S-propargyl-cysteine Biopharmaceutics classification system dissociation constant equilibrium solubility partition coefficient rat in situ perfusion