Abstract
Objectives: An orally administered anticancer drug has been poor drug absorption; drug resistance and metabolism, which alters the bioavailability of drugs. An in situ intestine perfusion technique is developing under the different perfusion rates in the presence of drug inducers and inhibitors of cytochrome isoenzyme-P (CYP)-3A4 and P-glycoprotein (P-gp) for drug concentrations.
 Materials and Methods: The modified in situ intestinal perfusion technique was developed and followed to obtain the portal and hepatic venous blood samples paralleled at different perfusion time and flow rates of 0.05, 0.1, 0.5, and 1.0 mL/min using the imatinib (1 mg/mL) drug alone and in the presence of drug inducer and drug inhibitor for the period of 3 h. The imatinib drug concentrations were assayed using high-pressure liquid chromatography.
 Results: The results reveal that the mean imatinib drug concentrations in portal vein were higher than hepatic vein at various perfusion flow rates and time intervals were observed. The area under curve and plasma drug concentrations maximum of imatinib alone absorptions were significantly different between portal and hepatic veins (p<0.05) at the flow rates of 0.5 and 1.0 mL/min and also in the presence of drug inducer and inhibitors that indicating for the considerable hepatic involvement in the presystemic extraction or metabolism of drugs.
 Conclusions: The in situ perfusions approach could provide the useful tool for improving the basic understanding of absorption kinetics and hepatic metabolism of drugs in the presence of drug inducers and drug inhibitors (CYP3A4 and P-gp) under the development and facilitating the clinical applications.
Highlights
Oral administered drugs have been more convenient, easy, and high patient compliance
The area under curve and plasma drug concentrations maximum of imatinib alone absorptions were significantly different between portal and hepatic veins (p
The in situ perfusions approach could provide the useful tool for improving the basic understanding of absorption kinetics and hepatic metabolism of drugs in the presence of drug inducers and drug inhibitors (CYP3A4 and P-gp) under the development and facilitating the clinical applications
Summary
Oral administered drugs have been more convenient, easy, and high patient compliance. If the administered drugs may not be reached into the systemic circulation until the large doses were given, the natural bioenhancers or plantbased molecules were reduced the risk of drug resistance, rapid metabolism of drugs, and minimize the drug toxicity and they can improve the oral bioavailability [3,4]. The oral bioavailability of imatinib drug always depends on the transporter proteins of P-gP and metabolic enzyme of CYP3A4. Curcumin is a natural phytochemical have been multifunctional agent, which is reduce the risk of cancer; in the combination of curcumin with imatinib can improve the pharmacokinetics and pharmacodynamic parameters of the drug [11]. We investigated the effects of curcumin on drug absorption and drug metabolism in the presence of drug inducers and drug inhibitors
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