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Ribavirin in Piglets in Vivo Pharmacokinetics and Toxicology

Author: LiuXueMei
Tutor: GaoYunSheng
School: Taishan Medical College
Course: Pharmacology
Keywords: pig ribavirin pharmacokinetics toxicologic effect cytotoxicity
CLC: R965
Type: Master's thesis
Year: 2010
Downloads: 57
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Abstract

ObjectiveThe aim of this study was to learn ribavirin in vivo drug metabolism of piglets. It was observed with oral ribavirin against swine vivo toxicity of ribavirin-prone pig poisoning on the reasons for the further study of mechanisms of porcine ribavirin poisoning theory basis for the safety of human drug ribavirin for reference.Methods1.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）.2.We investigated the toxic effect in pigs with different doses of ribavirin . 12 piglets were randomly divided into 4 groups including a control group and three experimental groups in order to investigate the toxic effect in piglets with different doses of ribavirin. Ribavirin was administered once daily for 10 consecutive days at a dose of either 10, 30, or 60 mg/kg. The toxic effects were observed by ethology, blood, serum, urine, bone marrow and pathologic changes before and after administation.3. Testing different doses of ribavirin on passage cells derived from pigs （PK cells） cytotoxicity, cytotoxicity by WST-1 kit, microscope cell disease.Result1. In single dose study, The pharmacokinetic result revealed it a double- departmentmodel and the kinetic parameters were t_1/2βwas （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 repeat- ed dose study, t_1/2Ke 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. 2. The results of this study in piglets 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 60mg/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..3. The study proved that ribavirin has toxic action to PK cell .TC50 was 1.89mg/mL. Cells showed degeneration and necrosis.Conclusion1. In this experiment, high performance liquid chromatography （HPLC） method of dynamic detection Ribavirin in piglets in vivo pharmacokinetic changes that pig single or multiple subjects after oral administration of ribavirin metabolites in pig plasma law.2. Established by oral administration of different doses of ribavirin piglets poisoning model, systematic observation of the clinical manifestations, pathophysiology and morphological changes in the initial ribavirin revealed the occurrence of side effects on the piglets and poisoning mechanism of the pathological characteristics of piglets.3. Application of WST-1 cytotoxicity assay kit and cell morphology to detect passage of ribavirin on the swine kidney cell toxicity caused by toxic concentrations, more than half of the initial understanding of the pathological changes of cells.4.Test confirmed that ribavirin on the expression in porcine tissues pan-addicted toxic to red blood cells, bone marrow cells, gastrointestinal epithelial cells and epithelial cells of the pancreas is most sensitive to toxic doses cause piglets and clinical cases of poisoning reported a greater difference in dose, speculated that clinical drug poisoning due to, among pigs and the occurrence of dose related, this may also pigs own health status, age and physiological state of the pathological changes of metabolism, diet and other factors related drugs.

Ribavirin in Piglets in Vivo Pharmacokinetics and Toxicology

Abstract

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