Genistein Exposure Interferes with Pharmacokinetics of Celecoxib in SD Male Rats by UPLC-MS/MS

Abstract

Objective To discuss the effects of genistein on the metabolism of celecoxib in vitro and in vivo. Method In vitro, the effects of genistein on the metabolism of celecoxib were studied using rat and human liver microsomes. In vivo, pharmacokinetics of celecoxib was evaluated in rats with or without genistein. Fifteen Sprague-Dawley (SD) rats were randomized into three groups: celecoxib (A group), celecoxib and 50 mg/kg genistein (B group), and celecoxib and 100 mg/kg genistein (C group). Single dose of 33.3 mg/kg celecoxib was orally administered 30 min after genistein ig. At 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after celecoxib administration, 300–400 µl blood samples were collected and the concentration of celecoxib was analyzed by ultrahigh-performance liquid chromatography-tandem mass spectrometry system. Result Genistein showed notable inhibitory effects on three microsomes. It affected pharmacokinetics of celecoxib in vivo experiments. Genistein had dramatically ability to suppress CYP2C9∗1 and ∗3. After pretreatment with genistein, AUC and Cmax of the C group were higher than B group. CLz/F of C group was lower than the B group. Conclusion Genistein inhibits the conversion of celecoxib in vitro and in vivo. So, the dosage of celecoxib should be adjusted if it was used associated with genistein.

Structural Modification of Nanomicelles through Phosphatidylcholine: The Enhanced Drug-Loading Capacity and Anticancer Activity of Celecoxib-Casein Nanoparticles for the Intravenous Delivery of Celecoxib

“…The extraction solution and pulverized cell residue were separated by centrifugation (10,000× g), and the supernatant was subjected to UPLC-MS/MS to determine intracellular CX. The UPLC-MS/MS analysis was performed according to the method reported by Zheng et al [24]. The UPLC system (Waters, Milford, MA, USA) equipped a binary solvent manager and a sample manager with a flow-through needle and a Waters XEVO TQD triple-quadrupole with an electrospray ionization source and a BEH C18 column (2.1 × 50 mm, 1.7 µm).…”

Effect of Andrographis paniculata extract and Andrographolide on the pharmacokinetics of Aceclofenac and Celecoxib in rats

“…Several bioanalytical methods have been developed for the determination of ACF and CXB in rats and humans [12][13][14][15]. Herb-drug interaction studies of CXB with Ojeok-san, and Genistein have been reported [16,17]. Bioanalytical methods are available for the determination of andrographolide alone and in combination with other drugs [18,19].…”