title: Pharmacokinetics of anti-HBV polyoxometalate in rats.
abstract: Polyoxometalates are non-nucleoside analogs that have been proven to exhibit broad-spectrum antiviral activity. In particular, Cs2K4Na[SiW9Nb3O40].H2O 1 shows low toxicity and high activity against HBV. The preclinical pharmacokinetics of Compound 1 in rats were characterized by establishing and applying inductively coupled plasma-mass spectrometry method to determine the concentration of W in plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method demonstrated good sensitivity and application in the pharmacokinetics study of polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or oral administration fit a two-compartment model. Tmax ranges from 0.1 h to 3 h and the T1/2 of Compound 1 is between 20 h and 30 h. The absolute bioavailability of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%, respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36 mg/ml of Compound 1 are 62.13±9.41%, 71.20±24.98% and 49.00±25.59%, respectively. Compound 1 was widely distributed throughout the body, and high levels of compound 1 were found in the kidney and liver. The level of Compound 1 in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile, respectively. For elaborate pharmacokinetic characteristics to be fully understood, the metabolism of Compound 1 needs to be studied further.
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qu
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Song
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Dehui
authors.initials: D
authors.lastname: Yin
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.affiliation: School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D017973:Tungsten Compounds / Q000493:pharmacokinetics*; D000099294:Polyoxometalates
chemical_list: D000998:Antiviral Agents; D017973:Tungsten Compounds; C102296:polyoxometalate I; D000099294:Polyoxometalates