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

Abstract

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 Cmax ~18.77%, AUC0–T ~28.07%, MRT ~16.87%, and Kel ~24.76%, and a significant decrease in the volume of distribution Vz/F_obs ~37.66%, the rate of clearance (Cl/F) ~21.81%, and T½ ~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.

Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism

“…A PierceTM BCA Protein Assay Kit (Thermo Fisher Scientific) was used to extract the total protein from the hepatic and intestinal tissues by bicinchoninic acid technique [ 39 ]. Immunoblots were executed as per the methods of Towbin et al (1979) with slight modification [ 40 , 41 , 42 ]. Briefly, 10% SDS polyacrylamide gels were used to electrophorese 25 μg of hepatic and intestinal epithelial proteins.…”

A Box-Behnken Design for Optimization of Ultrasound-Assisted Extraction of Sinapic Acid From Fragaria Ananassa

“…Several preclinical studies have investigated the pharmacokinetics and interaction of sinapic acid, revealing insights into its drug disposition in animal models [39,40]. These studies suggest that sinapic acid exhibits moderate bioavailability, with factors such as route of administration and dosage playing pivotal roles in its absorption and systemic availability [39][40][41]. This study aims to investigate the application of Box Behnken design for ultrasound assisted extraction of sinapic acid from Fragaria ananassa.…”