Pharmocokinetics Study In Rat Of HCV New Drug

Hepatitis C, caused by hepatitis C virus, led to a chronic liver inflammation, necrosis and fibrosis, and eventually develop into cirrhosis or hepatocellular carcinoma. The disease is prevalent worldwide, becoming a serious threat to society and the public. Diagonosed patients use long-acting interferon(PEG-IFN) and ribavirin combination therapy to treat, but the treatment effect is not ideal. A company successfully developed anti-hepatitis C drug by screening more than 100 kinds compounds and declared a class Xinhua drug application. Pharmacokinetic study is required as specified in the application materials project. Pharmacokinetic study is not only a discipline using mathematical methods to find out quantitative process rules in vivo of the drug, but also an essential project of drug development process. Drug kinetics, also known as non-clinical kinetics, did outstanding contributions in helping clarify characteristics of drug absorption, distribution, metabolism, elimination, founding drug transport law in the body, clarifying the relationship between drug efficacy and toxicity, or the relationship between the drug concentration in vivo drug accumulation section and accumulation degree, clarifying the law to improve the bioavailability, guiding the new formulation design and renovation, discovering the relationship structure-activity relationship between the structure and metabolism and elimination rate, etc. Systematic and comprehensive non-clinical pharmacokinetics studies in drug discovery process can clarify the mechanism of its efficacy and toxicological effects and provide a reference and an important basis medication of future clinical trial design and first dose. In vivo pharmacokinetics in rats is one of the most important part of preclinical drug development process. In this study, according to Chinese Pharmacopoeia and the Food and Drug Administration about the new drug application requirements, SPF rats were used as experimental animals, the establishment of jugular vein cannulation animal model, bile duct intubation animal models, using liquid mass spectrometry from the new drugs in rat in vivo pharmacokinetics, tissue distribution and excretion test three aspects, collecting plasma, tissue, feces, urine and bile rat plasma concentration, and the results were compared with the intended function, its new drug the basis for approval and clinical trials.The experimental results are as follows:1. DMPK characteristic of HCV new drug after oral administration in SD rats showed that pharmacokinetics oral bioavailability is about 34%, showing a non-linear relationship between dose and exposure, the elimination half-life time is 2.08 hours, HCV new drug showed no significant gender differences in pharmacokinetics study; Exposition of HCV new drug in continuous administration of 7 days had no significant accumulation in rats;2. Tissue distribution study showed that HCV new drug eliminate quickly in most organs, suggesting that the compound have less tendency to accumulate,which indicate that new drug is susceptible to HCV protein binding effect of the drug to produce the drug- drug interactions;3. HCV new drug mainly excreted through feces in the form of prototype drug.Research Conclusion: In pre-clinical studies of HCV new drugs, the pharmacokinetics parameter obtained from SD rats can be used as important reference for predicting HCV new drugs in the human body pharmacokinetic behavior, providing clinical experimental design of clinical drug trials and an important basis for first dose.