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Pharmacokinetic effects of capsaicin on vinblastine in rats mediated by CYP3A and Mrp2
Author(s) -
Zhai Xuejia,
Feng Yiming,
Liu Jun,
Li Jie,
Zong Yan,
Tuo Zhan,
Gao Shenrong,
Lv Yi
Publication year - 2019
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12448
Subject(s) - multidrug resistance associated protein 2 , pharmacokinetics , capsaicin , ingestion , pharmacology , vinblastine , endocrinology , medicine , transporter , chemistry , atp binding cassette transporter , chemotherapy , biochemistry , receptor , gene
Abstract Capsaicin ( trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide , CAP) is an important ingredient in spicy foods consumed throughout the world. Vinblastine (VBL) is a naturally occurring alkaloid prescribed to cancer patients. Many cancer patients treated with VBL were taking CAP at the same time. This study attempted to investigate the effect of CAP on the pharmacokinetics of VBL, which is the substrate of CYP3A, P‐gp, and Mrp2. CAP, cyclosporine (CsA) or olive oil was given to rats for seven consecutive days, and on the seventh day, VBL (1.3 mg/kg) was administered intravenously. CsA was used as a CYP3A1/2 and transporter inhibitor, and olive oil was used as a vehicle. The results showed that pretreatment of rats with CAP (3.0 mg/kg) for seven consecutive days resulted in an increase in the AUC 0–t of VBL of about 29.8% ( P < 0.05) compared with the control group. Moreover, CAP decreased the CL of VBL to 75.5% ( P < 0.05). At this time, CYP3A1/2 and Mrp2/Abcc2 in the liver was decreased at the mRNA and protein levels. These results demonstrate that chronic ingestion of CAP will increase systemic exposure and reduce clearance of VBL in rats. The food–drug interaction between CAP and VBL appears to be due to modulation of CYP3A1/2 and Mpr2 expression by CAP.