oatp1b1基因多态性与利福平临床肝毒性的关联分析-association between oatp 1b1 gene polymorphism and clinical hepatotoxicity of rifampin.docx

AbstractAbstractIVIVABSTRACTBackground: Rifampicin is a commonly used first-line anti-TB drugs, with a large toxic of liver cells, when it combines with isoniazid and pyrazinamide used for anti-TB, the liver damage occurrence rate was 40.4%. OATP1B1 is the most important one in hepatic uptake transporters, involving in a variety of endogenous and exogenous substances drug to uptake and transport. OATP1B1 own the genetic polymorphisms, the one which has certain alleles has lower transport capacity that will affects the pharmacokinetics and pharmacodynamics process of various drugs, OATP1B1 gene polymorphism was related to side effects of drug and interactions effects of drugs. Rifampicin was the specific substrate of OATP1B1, primarily through the OATP1B1 which in the surface of liver cell membrane transported into the liver cells. Has been reported, the plasma concentration of rifampicin lower, the toxicity of liver was higher; the plasma concentration of rifampicin higher, the toxicity of liver was lower. We will presume that there are closely related between liver toxicity of rifampicin and the OATP1B1-mediated liver rifampicin drug concentrations. OATP1B1 have been confirmed the presence of gene polymorphisms, whether the toxicity of rifampicin in different individuals correlated with OATP1B1 gene polymorphisms, there were no researched and worth further discussion.Objective: This topic choice taking rifampicin liver damage of TB patients and take the same doses not present patients with liver damage, respectively to investigate OATP1B1 genetic polymorphism, rifampicin blood drug concentration, and the mutual relationship between liver toxicity, liver from drug transporter molecular level to clarify the occurrence of rifampicin liver toxicity mechanism, to guide clinical rational drug use and experiment and scientific basis for prevention and treatment of hepatic toxicity.Methods:To collect general information of TB patients with , the treatment condition by usin