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Publications (2)3.71 Total impact

  • Article: 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.
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    ABSTRACT: (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 (∼35.87%) within 36 h. Two main metabolites are the hydroxylation product and the glucuronide conjugate of the hydroxylation product.
    Pharmacology 03/2012; 89(3-4):192-200. · 1.79 Impact Factor
  • Article: Pharmacokinetics, tissue distribution, and plasma protein binding study of platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats and dogs by ICP-MS.
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    ABSTRACT: Dicycloplatin, as a new antitumor supramolecule, was considered to have higher solubility and higher stability compared with carboplatin. The aim of the present study was to evaluate the pharmacokinetic characteristics of platinum originating from dicycloplatin. A rapid, sensitive, and specific method with inductively coupled plasma mass spectrometry (ICP-MS) has been developed for the determination of platinum in bio-samples. The study was performed in male rats and dogs at a single dose of 10 and 5 mg kg(-1) separately by intravenous injection. Pharmacokinetic parameters were calculated by non-compartmental method, and the dose of platinum was used in the calculation of these parameters. Results showed that plasma concentrations of platinum began to decrease rapidly initially but decline slowly with a long terminal phase. The mean half-life was 27.39 and 100.98 and clearance was 0.77 and 0.08 L/h/kg for rats and dogs separately. Tissue distribution showed that platinum originating from dicycloplatin had a certain distribution in testis and prostate. Plasma protein binding proportion of platinum was increased with time. In conclusion, this research investigated the pharmacokinetic characteristics including plasma kinetics, tissue distribution, and plasma protein binding of platinum originating from dicycloplatin in rats and dogs in detail for the first time by ICP-MS.
    Biological trace element research 02/2012; 148(2):203-8. · 1.92 Impact Factor