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 Resveratrol stereoselectively affected (±)warfarin pharmacokinetics and enhanced the anticoagulation effect

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tse-Yin Huang ◽  
Chung-Ping Yu ◽  
Yow-Wen Hsieh ◽  
Shiuan-Pey Lin ◽  
Yu-Chi Hou
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Systemic Exposure ◽  
International Normalized Ratio ◽  
Therapeutic Window ◽  
Cancer Resistance ◽  
Parallel Design ◽  
Concurrent Use ◽  
Resistance Protein ◽  
Conjugated Metabolites

Abstract Resveratrol (RVT) has various beneficial bioactivities and popularly used as a dietary supplement. RVT showed inhibitions on CYP1A2/2C9/3A4, breast cancer resistance protein (BCRP), and some conjugated metabolites of RVT also inhibited BCRP. (±)Warfarin, an anticoagulant for cardiovascular disease but with narrow therapeutic window, were substrates of CYP1A2/3A4(R-form), 2C9(S-form) and BCRP. We hypothesized that the concurrent use of RVT might affect the metabolism and excretion of warfarin. This study investigated the effect of RVT on the pharmacokinetics and anticoagulation effect of (±)warfarin. Rats were orally given (±)warfarin (0.2 mg/kg) without and with RVT (100 mg/kg) in a parallel design. The results showed that RVT significantly increased the AUC0−t of S-warfarin and international normalized ratio. Mechanism studies showed that both RVT and its serum metabolites (RSM) inhibited BCRP-mediated efflux of R- and S-warfarin. Moreover, RSM activated CYP1A2/3A4, but inhibited CYP2C9. In conclusion, concomitant intake of RVT increased the systemic exposure of warfarin and enhanced the anticoagulation effect mainly via inhibitions on BCRP and CYP2C9.

scholarly journals Phytoestrogens/Flavonoids Reverse Breast Cancer Resistance Protein/ABCG2-Mediated Multidrug Resistance

2004 ◽  
Vol 64 (12) ◽  
pp. 4346-4352 ◽  
Author(s):  
Yasuo Imai ◽  
Satomi Tsukahara ◽  
Sakiyo Asada ◽  
Yoshikazu Sugimoto
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
Resistance Protein
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