Cytochrome P450 (CYP) enzymes are important for drug metabolism. They chemically modify drugs to make them more soluble, which allows the drugs to be excreted from the body. Of the 30 CYP enzymes, 6 (CYP1A2, 2C9, 2C19, 2D6, 2E1, 3A4/5) are of clinical interest because these enzymes are the key players in drug metabolism. Differences in genetics lead to individuals of the same species expressing different CYP enzymes. The different combination of CYP enzymes may affect the rate of drug metabolism or produce metabolites that may cause adverse side effects. Predicting drug metabolites and drug-drug interactions is important when designing and prescribing new drugs because other drugs can act as CYP activators or inhibitors. Duloxetine is an antidepressant mainly metabolized by CYP1A2 and CYP2D6 isotypes. In this experiment, Duloxetine was metabolized using rat microsomes, housing a variety of CYP isotypes. Efficiency of metabolism in the presence and absence of inhibitors was measured using HPLC-MS.
Research Report, Final Report Form