Abstract
The cytochrome P450 enzyme family is the most abundant and responsible for the metabolism of more than 60% of currently marketed drugs and is considered central in many clinically important drug interactions. Seven different grapefruit and pummelo juices as well as 5 furocoumarins isolated from grapefruit juice were evaluated at different concentration on cytochrome P450 3A4 (CYP3A4), cytochrome P450 2C9 (CYP2C9), and cytochrome P450 2D6 (CYP2D6) isoenzyme activity. Grapefruit and pummelo juices were found to be potent inhibitors of cytochrome CYP3A4 and CYP2C9 isoenzymes at 25% concentration, while CYP2D6 is inhibited significantly low at all the tested concentration of juices (P < 0.05). Among the 5 furocoumarins tested, the inhibitory potency was in the order of paradisin A > dihydroxybergamottin > bergamottin > bergaptol > geranylcoumarin at 0.1 microM to 0.1 mM concentrations. The IC(50) value was lowest for paradisin A for CYP3A4 with 0.11 microM followed by DHB for CYP2C9 with 1.58 microM.
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