P Glycoprotein Mediated Drug Interaction between Digoxin and Orange Juice- Exploratory Study by In-vitro Approach

Abstract

P.gp is an efflux transporter that plays a vital role in drug transportation. Aim: This exploratory study is aimed to find the P-glycoprotein (P-gp) mediated drug interaction between digoxin and orange juice, conducted for a period of six months. The 3D structure of the human P-gp was predicted from the peptide by molecular threading using default settings. The structural analysis and verification server and the PDB were used to assess the stereo-chemical quality of these structures. The molecular structure of P-gp in a transport cycle has been investigated using a variety of methods. Molecular docking has been performed to predict the highest binding affinity to P gp with ligands of orange juice and ligands of ketoconazole. In 50% ethyl acetate extract of orange juice was prepared and a transcellular transport study was done using MDR1 transfectants and MRP2 transfectants LLC-PK1, LLC-GAS-COL150, LLC-pCI and LLC-MRP cells grown in M199 medium supplemented with 10% fetal calf serum at 37℃ in a humidified atmosphere of 5% CO2/95% air. The minimum inhibitory concentration is found to be 125 mcg/mL. Hence, the loading concentration along with orange juice is found to be 24.562 mcg/mL and the concentration less than that is found with poor sensitivity. Whereas the concentration above 125 mcg/mL loaded with orange juice is found to inhibit P-gp. The absorbance of orange juice and digoxin was measured at 470 nm. Since digoxin is not sensitive to orange juice beyond the concentration of 125 mcg/mL, it is considered as the MIC. Hence orange juice is a moderate p-gp Inhibitor and it escalates the serum digoxin toxicity. Orange juice is inhibiting the P-gp which increases the serum toxicity levels of digoxin.