The Study On Acute Toxicity And Pharmacokinetics Of Avolix200in Mice

ObjectiveTo establish the method of determining concentration of Avolix200in serum and the tissue by HPLC. To analyze the pharmacokinetics and tissue distribution of Avolix200following intraperitoneal injection in mice. To evaluate the safety of Avolix200prospectively by acute toxicity assay in mice.MethodsAvolix200was administered to mice at the dose of50mg/kg,100mg/kg and200mg/kg respectively by intraperitoneal injection. Blood were collected at the point of0、3、6、9、15、20、40、60、90、120、180、240and300min after injection of Avolix200. Protein was precipitated by adding acetonitrile and the Avolix200were extracted from serum samples. The Intertex C18column was used, the detection was carried out at230nm with UV detector, the mobile phase consisted of phosphoric acid solution (pH3.0):acetonitrile (50:50V/V) delivered at a flow rate of1mL·min-1.Avolix200were administered by intraperitoneal injection to mice at the dose of50mg/kg,100mg/kg and200mg/kg respectively. Executed the mice and collected the tissues (heart, liver, kidney, lung) at3、6、9、15、40、60and120min after injection. The tissue homogenate were prepared, the tissue concentration of Avolix200were determined by the same method as above.The toxic symptoms and number of dead mice were observed for seven days after single intraperitoneal dosing of Avolix200in mice.ResultsSerum Samples were collected at various time after injection of Avolix200, The pharmacokinetic profile of Avolix200were determined in mice. It was shown to fit opening one-compartment nonlinear pharmacokinetic model. There were significant differences in the pharmacokinetics parameters between the three dosages (P<0.01); The concentration of Avolix200in the tissue could be determined quickly after injection. The peak time extended along with the increase of administration dosage; there were no differences in the drug concentration between the four tissues at50mg/kg and100mg/kg dosages; the highest concentration was found in lung at200 mg/kg dosage (p<0.05).When Avolix200was administered intraperitoneally, the median lethal dose (LD50) was771.73mg/kg in mice and its95%confident interval was729.73816.15mg/Kg. Conclusion1We have established an HPLC method using UV detection. The method can be used for pharmacokinetic determinations at all relevant doses of Avolix200.2Avolix200are administered by intraperitoneal injection to mice at the dose of50mg/kg,100mg/kg and200mg/kg respectively, the pharmacokinetic behavior is found to fit one-compartment nonlinear pharmacokinetic model.3Avolix200are administered by intraperitoneal injection to mice at the dose of50mg/kg,100mg/kg and200mg/kg respectively, there were no differences in the drug concentration between the four tissues at50mg/kg and100mg/kg dosages, but the highest concentration is found in lung at200mg/kg dosage.4The LD50of Avolix200is771.73mg/kg in mice, it is safe at therapeutic dose.