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.

Differentiation of stem cells into insulin‐producing cells under the influence of nanostructural polyoxometalates

“…POMs are nanocompounds of great interest for chemical research, but their biomedical applications have also been extensively studied in the last few decades. Developing innovative and “smart” nanocompounds exhibiting effective antiviral (Rhule et al ., ; Wang et al ., ), antibacterial (Inoue et al ., , ) and antitumor effects (Ogata et al ., ; Prudent et al ., ) could provide an alternative approach to conventional treatments of the most serious threats to human health (such as cancer or infectious diseases). An important direction in the study of POMs concerns the potential treatment of diabetes.…”

Antiviral effects of a niobium‐substituted heteropolytungstate on hepatitis B virus‐transgenic mice

“…Transgenic mice represent a suitable and widely used system for the study of in vivo activity of anti‐HBV agents and their toxicity (Wang, Liu, et al, ; Wang, Qu, et al, ; Zhang et al, ). At the beginning of the experiment, we examined the plasma HBV DNA and HBsAg, liver tissue HBV RNA at four transgenic mice.…”

“…Treatment of HepG2.2.15 cells with this compound effectively suppressed the secretion of HBV antigens and HBV DNA in a dose‐dependent and time‐dependent manner. IC 50 values were determined to be 80 μmol/L for HBsAg, 75 μmol/L for HBeAg, and 3.72 μmol/L for supernatant HBV DNA at Day 9 postexposure (Wang et al, ; Wang et al, ; Zhang et al, ). Pharmacokinetics was characterized in rats after intravenous or oral administration and was found to fit a two‐compartment model.…”

“…Pharmacokinetics was characterized in rats after intravenous or oral administration and was found to fit a two‐compartment model. High levels of the compound were found in the kidney and liver (Wang, Liu, et al, ; Wang, Qu, et al, ). The above results suggest that Cs 2 K 4 Na[SiW 9 Nb 3 O 40 ]·H 2 O inhibited HBV replication.…”

Genotoxicity and acute and subchronic toxicity studies of a bioactive polyoxometalate in Wistar rats

“…A series of antiviral and biochemical experiments was performed for screening, and it was found that a Keggin-type of POM with the formula of Cs 2 K 4 Na[SiW 9 Nb 3 O 40 ] (POM93) possessed high anti-hepatitis B virus (anti-HBV) [6, 21] and anti-hepatitis C virus (anti-HCV) [22] activities with low cytotoxicity on MDCK, Vero, and MT-4 cells. Limited knowledge is available regarding the effects of POMs on human physiology.…”