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.
Department of Clinical Pharmacy, School of Pharmacy, Fudan University , Shanghai , People's Republic of China .
Guo
G
Ma
Lin
L
Zhang
Peng
P
Zhang
Xingfei
X
Bao
Ning
N
Zhou
Qingling
Q
Shi
Yuanting
Y
Zheng
Hongrui
H
Liu
Fengjiao
F
Bu
Ying
Y
Zhang
Wenjie
W
Huang
Fen
F
Wang
Yizhun
Y
Zhu
Weimin
W
Cai
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D055598:Chemical Phenomena; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D065569:Gastrointestinal Absorption; D006863:Hydrogen-Ion Concentration; D008297:Male; D023421:Models, Animal; D010539:Permeability; D017207:Rats, Sprague-Dawley; D012995:Solubility; D053719:Tandem Mass Spectrometry
D000970:Antineoplastic Agents; C556437:S-propargylcysteine; D003545:Cysteine
Biopharmaceutics classification system; S-propargyl-cysteine; dissociation constant; equilibrium solubility; gastrointestinal absorption; partition coefficient; physicochemical characteristics; rat in situ perfusion