الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Chronic hepatitis C is considered as a main cause of death, and morbidity that affects up to 185 million people around the world, and Egypt has the highest prevalence rate in the world. chronic hepatitis C is frequently progresses to cirrhosis, end-stage liver disease, hepatocellular carcinoma, and death. There are vaccines to prevent hepatitis A and hepatitis B; however, there is no vaccine for hepatitis C. Daclatasvir is a new oral first in class direct acting antiviral agent which binds to and inhibits the function of the hepatitis C virus protein NS5A. Daclatasvir is reported to have a limited oral bioavailability, one of the possible reasons its affinity for P-glycoprotein (P-gp) transporters as it is a substrate for it and substrate for organic cation transporter 1 (OCT 1). Daclatasvir is also a substrate of CYP3A metabolizing enzymes, CYP3A4 is the main CYP isoform accountable for the daclatasvir metabolism which is present in liver, intestinal lumen, and gut wall. Consequently, the plasma concentration and the antiviral activity can be affected when co-administered with P-gp transporter inhibitors, inducers and drugs which can alter the function of CYP3A4. The intestinal P-gp efflux transporter has an important role in limiting intestinal absorption of orally absorbed drugs. P-glycoprotein efflux system and CYP3A4 enzyme system reduce bioavailability of drugs that enter the intestinal mucosa. Although these drugs technically are absorbed, they may not be bioavailable. If the pglycoprotein efflux and CYP3A4 metabolic systems could be selectively and reversibly inhibited, the bioavailability of many orally absorbed drugs could be dramatically increased A lot of dietary components are inhibitors of P-gp efflux transporters. One of those constituents is piperine, the active constituent of black pepper, which is a known P-gp inhibitor. Gastric acid blockers are frequently used among HCV infected patients as gastric acid related disorders are common in HCV patients. Omeprazole, a proton pump inhibitor, is one of the most utilized drugs worldwide. It is reported that omeprazole is the eleventh most used medication in HCV infected patients. Omeprazole is an in vivo suppressant of CYP3A4 and CYP2C19. In addition, Omeprazole is reported to cause significant pharmacokinetic drug interactions due to P-gp inhibition. The aim of this thesis was to investigate the membrane transport parameters of daclatasvir from different anatomical sites of rabbit intestine. Another major objective of this research was to examine the influence of piperine and omeprazole on the regional absorption of daclatasvir from rabbit intestine. In order to achieve these objectives, a constant rate in situ single pass intestinal perfusion technique was adopted, utilizing the rabbit as an animal model. Thus, the work in this thesis comprises the following sections.