| Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide),a broad-spectrum antiviral agent structurally related to guanosine, has activity in vitro against both RNA and DNA viruses.. In recent years, ribavirin are widely used in the prevention and treatment of swine's disease because of spreading of the high swine fever. Poisoning cases in human and pigs have occurred caused by administration of ribavirin. The safety issues of ribavirin are questioned.The structure of Pig's organs and physiological characteristics is very similar to human.It is importance to protect the safety of human's life and to evaluate the drug's toxicity.High performance liquid chromatorgraphic method(HPLC) to detect ribavirin in Pigs Plasma were developed. Pharmacokinetics of ribavirin were investigated. Following oral administration at single or repeated dose of 90mg/kg body weight in healthy Pigs(n=3). Chromatography separation was aehieved. In single dose study, The pharmacokinetic result revealed it a double-departmentmodel and the kinetic parameters were t1/2βwas (23.50±3.95)h, CL(s) was (1.97±0.55) L·kg-1·h-1 and V/F(c)was (33.09±6.77) L·kg-1. In repeated dose study, t1/2Ke was (21.74±25.41)h, CL(s) was (0.73±0.74) L·kg-1·h-1 and V/F(c)was (9.11±3.24) L·kg-1.It indicated that ribavirin was absorbed and distributed rapidly, eliminated slowly and showed large volume of distribution in pig with administration.We investigated the toxic effect in pigs with different doses of ribavirin . 12 pigs were randomly divided into 4 groups including a control group and three experimental groups in order to investigate the toxic effect in pigs with different doses of ribavirin. Ribavirin was administered once daily for 10 consecutive days at a dose of either 10, 30, or 90 mg/kg. The toxic effects were observed by ethology, blood, serum, urine, bone marrow and pathologic changes before and after administation. The results of this study in pigs indicated that there was no intoxicated significant change between experimental groups that daily administration of ribavirin at a dose range of 10mg/kg and control group,but daily administration of ribavirin at a dose range of 30 to 90mg/kg induced a dose-related toxic effect. toxic effect show that pantropic toxicity and pathological changes on blood, bone marrow, gastrointestinal tract, pancreas, heart, liver, kidneyand brain.Hemolytic anemia is the primary mechanism for the pathogenesis of pig poisoning, the reasons which result in loss of appetite and constipation are that Catarrhal inflammation and necrotizing inflammation of gastrointestinal tract and pancreatopathy. In summary, high doses of ribavirin side-effects will increase the risk of death of pig infected.PK cell which was injected ribavirin was measured by WST-1 cell proliferation and cytotoxicity assay kit. cytotoxicity was observed by inverted microscope, Cells growing on cover slip was observed by light microscope.The study proved that stagnation of medicine cause intoxication.In a word,toxic effect show that pantropic toxicity and pathological changes on blood, bone marrow, gastrointestinal tract, pancreas, heart, liver, kidneyand brain. dosis toxica in experiment is different from dosis toxica in clinic.it proved that health status,age,physiological state, animal feeds and Medication dosage result in death after intoxication of pigs. |
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