scholarly journals Bidirectional Influences of Cranberry on the Pharmacokinetics and Pharmacodynamics of Warfarin with Mechanism Elucidation

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3219
Author(s):  
Chung-Ping Yu ◽  
Meng-Syuan Yang ◽  
Pei-Wen Hsu ◽  
Shiuan-Pey Lin ◽  
Yu-Chi Hou
Keyword(s):  
Breast Cancer Resistance Protein ◽  
Plasma Concentrations ◽  
Therapeutic Index ◽  
Cancer Resistance ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Narrow Therapeutic Index ◽  
Combined Use ◽  
Ingestion Time ◽  
Resistance Protein ◽  
Metabolizing Enzyme

Cranberry is a dietary supplement popularly used for the prophylaxis of urinary tract infection. Interestingly, cranberry–warfarin interactions in clinical reports have shown bidirectional outcomes. (±) Warfarin, a widely prescribed anticoagulant, but with a narrow therapeutic index, contains equal amounts of S- and R-warfarin, of which S-warfarin is more active. The aim of this study was to investigate the effects of different ingestion times of cranberry on the pharmacokinetics and pharmacodynamics of warfarin. Rats were orally administered (±) warfarin (0.2 mg/kg) with and without cranberry (5.0 g/kg) at 0.5 h prior to the warfarin, and at 10 h after the warfarin. The plasma concentrations of S- and R-warfarin were determined by LC/MS. The results indicate that cranberry ingested at 0.5 h before (±) warfarin significantly decreased the systemic exposures of S-warfarin and R-warfarin. Conversely, when cranberry was ingested at 10 h after (±) warfarin, the elimination of S-warfarin was significantly inhibited, and the anticoagulation effect of (±) warfarin was significantly enhanced. The results of the mechanism studies indicate that cranberry activated the breast cancer resistance protein (BCRP), which mediated the efflux transports of S-warfarin and R-warfarin. Moreover, the metabolites of cranberry inhibited cytochrome P450 (CYP) 2C9, the main metabolizing enzyme for S-warfarin. In conclusion, cranberry affected the pharmacokinetics of (±) warfarin in a bidirectional manner by activating the BCRP by CJ during absorption and inhibiting the BCRP and CYP2C9 by CMs during elimination, depending on the ingestion time of CJ. The combined use of cranberry with warfarin should be avoided.

scholarly journals Febuxostat, But Not Allopurinol, Markedly Raises the Plasma Concentrations of the Breast Cancer Resistance Protein Substrate Rosuvastatin

2020 ◽  
Vol 13 (6) ◽  
pp. 1236-1243 ◽  
Author(s):  
Minna Lehtisalo ◽  
Jenni E. Keskitalo ◽  
Aleksi Tornio ◽  
Outi Lapatto‐Reiniluoto ◽  
Feng Deng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Plasma Concentrations ◽  
Cancer Resistance ◽  
Protein Substrate ◽  
Resistance Protein

scholarly journals Folium Sennae Increased the Bioavailability of Methotrexate through Modulation on MRP 2 and BCRP

2021 ◽  
Vol 14 (10) ◽  
pp. 1036
Author(s):  
Chung-Ping Yu ◽  
Yu-Hsuan Peng ◽  
Ching-Ya Huang ◽  
Yow-Wen Hsieh ◽  
Yu-Chi Hou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Systemic Exposure ◽  
Cancer Resistance ◽  
Parallel Design ◽  
Dosage Regimens ◽  
Combined Use ◽  
Associated Proteins ◽  
Resistance Protein

Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC0–2880, AUC720–2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC720–2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP.

scholarly journals Differential Effects of Chrysin on Nitrofurantoin Pharmacokinetics Mediated by Intestinal Breast Cancer Resistance Protein in Rats and Mice

2009 ◽  
Vol 12 (2) ◽  
pp. 150 ◽  
Author(s):  
Atsushi Kawase ◽  
Yukako Matsumoto ◽  
Motoshi Hadano ◽  
Yui Ishii ◽  
Masahiro Iwaki
Keyword(s):  
Breast Cancer ◽  
Small Intestine ◽  
Breast Cancer Resistance Protein ◽  
Plasma Concentrations ◽  
Mrna Levels ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Metabolizing Enzymes ◽  
Resistance Protein ◽  
Rats And Mice

PURPOSE: The activities of breast cancer resistance protein (Bcrp/ABCG2) as well as P-glycoprotein (P-gp) and drug-metabolizing enzymes can be inhibited by several flavonoids or drugs in rats. However, the species, gender and regional differences of effects of flavonoids on Bcrp/ABCG2 in rats and mice remain unclear, although Bcrp, like P-gp, is also important in controlling drug absorption and disposition. METHODS: We used chrysin as a model flavonoid because it possesses anti-inflammatory and antioxidative properties and is used as a dietary supplement. We examined the pharmacokinetics of nitrofurantoin, a specific Bcrp substrate, in rats and mice treated with chrysin. Bcrp mRNA levels were measured in liver, kidney, duodenum, jejunum and ileum in rats and mice. RESULTS: Plasma concentrations of nitrofurantoin were increased in rats, but not mice, treated with oral chrysin, compared with untreated controls. Intraperitoneal injection of chrysin into rats or mice had little effect on the elimination of nitrofurantoin, compared with untreated animals. CONCLUSIONS: These results suggest that chrysin-nitrofurantoin interactions occur in the small intestine in rats, but not in mice, possibly due to the higher levels of Bcrp expression in the small intestine in rats, compared with those in mice.

Breast Cancer Resistance Protein: A Potential Therapeutic Target for Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Sonali Mehendale-Munj
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Protein A ◽  
The Body ◽  
Cancer Therapies ◽  
Cancer Resistance ◽  
Lung Cancers ◽  
Resistance Protein ◽  
Atp Regulation ◽  
Treatment Procedures

: Breast Cancer Resistance Protein (BCRP) is an efflux transporter responsible for causing multidrug re-sistance(MDR). It is known to expel many potent antineoplastic drugs, owing to its efflux function. Efflux of chemothera-peutics because of BCRP develops resistance to manydrugs, leading to failure in cancer treatment. BCRP plays an important role in physiology by protecting the organism from xenobiotics and other toxins. It is a half-transporter affiliated to theATP-binding cassette (ABC) superfamily of transporters, encoded by the gene ABCG2 and functions in response to adenosine triphosphate (ATP). Regulation of BCRP expression is critically controlled at molecular levels which help in maintaining the balance of xenobiotics and nutrients inside the body. Expression of BCRP can be found in brain, liver, lung cancers and acute myeloid leukemia (AML). Moreover, it is also expressed at high levels in stem cells and many cell lines. This frequent expression of BCRP has an impact on the treatment procedures and if not scrutinized may lead to failure of many cancer therapies.

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