Pharmacokinetic, Distribution, Metabolism, and Excretion of (Z)-2-Amino-1,5-Dihydro-1-Methyl-5-[4-(Mesyl)Benzylidene]-4H-Imidazol-4- One Mesilate (ZLJ-601) in Sprague-Dawley Rats

作者：Zhang, Lingli; Li, Ning; Lai, Yisheng; Zhang, Yihua; Chen, Xijing^*; Chen, Li; Ji, Hui; Li, Cuiyun

来源：Pharmacology, 2012, 89(3-4): 192-200.

DOI：10.1159/000334931

• Pharmacokinetic
• ZLJ-601
• Tissue distribution
• Metabolism
• Excretion
• COX/5-LOX inhibitor

(Z)-2-amino-1,5-dihydro-1-methyl-5-[4-(mesyl)benzylidene]-4H-imidazol-4-one mesilate (ZLJ-601) is an imidazolone COX/5-LOX inhibitor, which has excellent anti-inflammatory activity with an improved gastrointestinal safety profile. The purpose of this study was to evaluate the in vivo absorption, distribution, metabolism, and excretion of ZLJ-601 in Sprague-Dawley rats. After intravenous or intragastric administration to rats, the concentration of ZLJ-601 in plasma, bile, urine, feces and various types of tissues was detected by LC-MS. We also conducted the identification of metabolites using tandem mass spectrometry. After the intravenous administration, the t(1/2) ranged from 38.71 to 42.62 min and the AUC increased in a dose-proportional manner. After oral dosing, the plasma level of ZLJ-601 peaked at 28.33 min, having a C-max value of 0.26 mg/l, and the bioavailability was only 4.92%. The highest tissue concentration of ZLJ-601 was observed in lung and kidney, but it was not found in brain. The majority of unchanged ZLJ-601 was excreted in urine (similar to 35.87%) within 36 h. Two main metabolites are the hydroxylation product and the glucuronide conjugate of the hydroxylation product.

• 出版日期2012
• 单位中国药科大学