Evaluation of lentinan effects on cytochrome P450 activity in rats by a cocktail method

In this study, a cocktail of probe drugs was used to assess whether lentinan could influence the activities of rat enzymes CYP3A4, CYP2D6, CYP1A2, CYP2C19, and CYP2C9 in vivo. Fourteen days after intraperitoneal injection of lentinan, rats were given an oral dose of a cocktail solution containing phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam. Then, we obtained blood in specific durations for the determination of plasma concentration of the probe drugs using UPLC-MS/MS. We also evaluated the pharmacokinetic parameters using the DAS 2.0 software. We found that various concentrations of lentinan increased the activity of rat CYP1A2, CYP3A4, CYP2D6, and CYP2C19 but not CYP2C9. These findings suggest that clinical application of lentinan combination with CYP3A4, CYP1A2, CYP2C19, or CYP2D6 should be given careful consideration as this may lead to herb-drug interactions and hence treatment failure.