title: Preclinical assessment of the distribution, metabolism, and excretion of S-propargyl-cysteine, a novel H2S donor, in Sprague-Dawley rats.
abstract: OBJECTIVE
  To study the distribution, metabolism and excretion of S-propargyl-cysteine (SPRC), a novel hydrogen sulfide (H2S) donor, after oral administration in rats.
  
  
  METHODS
  Adult Sprague-Dawley rats were used. The tissue distribution of [(35)S] SPRC-derived radioactivity was measured using a liquid scintillation counter. The plasma protein binding of SPRC was examined using 96-well equilibrium dialysis. The excretion of SPRC in urine, bile and feces was analyzed using the LC-MS/MS method. The major metabolites in rat biomatrices were identified using MRM information-dependent, acquisition-enhanced product ion (MRM-IDA-EPI) scans on API 4000QTrap system.
  
  
  RESULTS
  After oral administration of [(35)S]-SPRC at a dose of 75 mg/kg, [(35)S] SPRC-derived radioactivity displayed broad biological distribution in various tissues of rats, including its target organs (heart and brain) with the highest in kidney. On the other hand, the binding of SPRC to human, rat and dog plasma protein was low. Only 2.18% ± 0.61% and 0.77% ± 0.61% of the total SPRC administered was excreted unchanged in the bile and urine. However, neither intact SPRC nor its metabolites were detected in rat feces. The major metabolic pathway in vivo (rat bile, urine, and plasma) was N-acetylation.
  
  
  CONCLUSIONS
  The preliminary results suggest that SPRC possesses acceptable pharmacokinetic properties in rats.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Yuan-ting
authors.initials: YT
authors.lastname: Zheng
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Zhu
authors.forename: Guo
authors.initials: G
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Tan
authors.forename: Jin-lian
authors.initials: JL
authors.lastname: Zhang
authors.forename: Hai-xing
authors.initials: HX
authors.lastname: Shen
authors.forename: Jia-lin
authors.initials: JL
authors.lastname: Xu
authors.forename: Yi-zhun
authors.initials: YZ
authors.lastname: Zhu
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Cai
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; C556437:S-propargylcysteine; D003545:Cysteine; D006862:Hydrogen Sulfide