Cytochrome P450 3A2 and PGP-MDR1-Mediated Pharmacokinetic Interaction of Sinapic Acid with Ibrutinib in Rats: Potential Food/Herb-Drug Interaction

Ibrutinib (IBR) metabolism (primarily by CYP3A enzyme) is the main route of excretion for IBR, which could lead to drug-drug/herb-drug interactions with herbal medicines, nutritional supplements, and other foods. Sinapic acid (SA) is a bioactive phytonutrient that is used as a dietary supplement to treat a variety of illnesses. Pharmacokinetic interactions may occur when IBR interacts with SA, which influences the pharmacokinetic processes such as absorption, distribution, metabolism, and excretion. Therefore, it is obligatory to investigate the safety apprehensions of such parallel usage and to evaluate the possible impact of SA on the pharmacokinetics of IBR and propose a possible interaction mechanism in an animal model. The IBR concentration in plasma samples was determined using a validated UHPLC-MS/MS method after administration of a single oral dosage of IBR (50 mg/kg) in rats with or without SA pretreatment (40 mg/kg p.o. each day for 7 days, n = 6). The co-administration of IBR with SA displayed significant increases in C-max similar to 18.77%, AUC(0-T) similar to 28.07%, MRT similar to 16.87%, and K-el similar to 24.76%, and a significant decrease in the volume of distribution Vz/F_obs similar to 37.66%, the rate of clearance (Cl/F) similar to 21.81%, and T-1/2 similar to 20.43%, respectively, were observed as compared to rats that were administered IBR alone, which may result in increased bioavailability of IBR. The metabolism of IBR in the liver and intestines is significantly inhibited when SA is given, which may lead to an increase in the absorption rate of IBR. These findings need to be investigated further before they can be used in clinical practice.

Automated summary

The study found that when Ibrutinib interacts with Sinapic acid, it may influence the pharmacokinetics of Ibrutinib and result in increased bioavailability. This may be due to the inhibition of IBR metabolism in the liver and intestines by SA.