[Analysis of the mechanisms of the drug-drug interaction from a view of pharmacogenomics].
A wide variety of transporters and enzymes are involved in the disposition and metabolism of therapeutic drugs. Any compounds interacting with these proteins may inhibit uptake, efflux and/or metabolism of drugs and therefore alter the bioavailability and/or clearance of them. Progress in pharmacogenomics throws light on the clarification of mechanisms on drug-drug interaction. Various mutation and polymorphisms in drug transporters and metabolic enzymes were identified and some of which alter function of the proteins. The steroid and xenobiotic receptor, SXR, coordinately regulated CYP3A4, a major drug metabolizing enzyme and P-glycoprotein, a broad-specificity efflux pump. Now we are in the face of new period of study on drug interaction. With the help of pharmacogenomics, it might be possible to someday predict, avoid or manipulate potential cause of drug-drug interactions.
Sai
Yoshimichi
Y
Faculty of Pharmaceutical Sciences, Kanazawa University.
Tsuji
Akira
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions / Q000235:genetics*; D016678:Genome; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009154:Mutation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D026901:Membrane Transport Proteins; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human