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

Processes

Khalid M. Alkharfy¹  Ajaz Ahmad¹  Muzaffar Iqbal²  Essam A. Ali²  Mohammad Raish³  Yousef A. Bin Jardan³  Fahad I. Al-Jenoobi³  Mudassar Shahid³  Abdul Ahad³  Mushtaq A. Ansari⁴ 

[1] Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;

关键词: ibrutinib;    sinapic acid;    pharmacokinetics;    pharmacodynamics;    drug interaction;   

DOI  :  10.3390/pr10061066

来源: DOAJ

【 摘 要 】

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 ~18.77%, AUC_0–T ~28.07%, MRT ~16.87%, and K_el ~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 T_½ ~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.

【 授权许可】

Unknown