Physicochemical characteristics and gastrointestinal absorption behaviors ofS-propargyl-cysteine, a potential new drug candidate for cardiovascular protection and antitumor treatment

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 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.

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

“…The extensive pharmacokinetic and absorption, distribution, metabolism, and excretion studies published with SPRC (e.g., Zheng et al, 2011Zheng et al, , 2012Ma et al, 2015) as well as the recent efforts aimed at further optimization via pharmaceutical routes, suggest that clinical translation has been considered; however, to our knowledge, clinical trials have not yet been initiated.…”

A novel dendritic mesoporous silica based sustained hydrogen sulfide donor for the alleviation of adjuvant-induced inflammation in rats

“…The short half-life(Ma et al. 2015 ) of SPRC could result in the excretion before fully reacted with CSE, which lead to an incomplete H 2 S release in vivo . However, a longer and higher release of SPRC from SPRC@DMSN could be observed compared with SPRC powder in vivo ( Figure 4 ).…”

“…As reported, the released SPRC would elevate H 2 S levels via the CSE/H 2 S pathway in vivo, (MA et al 2011;Zheng et al 2011) and this pathway was also verified again in our study. The short half-life (Ma et al 2015) of SPRC could result in the excretion before fully reacted with CSE, which lead to an incomplete H 2 S release in vivo. However, a longer and higher release of SPRC from SPRC@DMSN could be observed compared with SPRC powder in vivo (Figure 4).…”

The Preparation of a Novel Poly(Lactic Acid)-Based Sustained H2S Releasing Microsphere for Rheumatoid Arthritis Alleviation

“…The loaded drug (SPRC) was quantified by HPLC method, as reported with little modification [ 42 ]. Briefly, an Agilent 1200 series HPLC system (Santa Clara, CA, USA) was used to detect SPRC samples from physicochemical properties.…”