TY - JOUR AU - Zheng Yuan-ting AU - Zhu Jian-hua AU - Ma Guo AU - Zhu Qing AU - Yang Ping AU - Tan Bo AU - Zhang Jin-lian AU - Shen Hai-xing AU - Xu Jia-lin AU - Zhu Yi-zhun AU - Cai Wei-min PY - 2016 TI - Preclinical assessment of the distribution, metabolism, and excretion of S -propargyl-cysteine, a novel H 2 S donor, in Sprague-Dawley rats JF - Acta Pharmacologica Sinica; Vol 33, No 6 (June 2012): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - Aim: 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. Conclusion: The preliminary results suggest that SPRC possesses acceptable pharmacokinetic properties in rats. UR - http://www.chinaphar.com/article/view/5679