title: No effect on pharmacokinetics of tamoxifen and 4-hydroxytamoxifen by multiple doses of red clover capsule in rats.
abstract: Tamoxifen is used in clinical practice for breast cancer patients and to prevent osteoporosis. Red clover (Trifolium pratense) preparations are consumed worldwide as dietary supplements for relieving postmenopausal symptoms. In the present study we investigated the possible herb-drug interaction between red clover and tamoxifen in rats. 15 days pre-treatment with red clover did not alter the tamoxifen and its active metabolite 4-hydroxytamoxifen pharmacokinetics significantly (p > 0.05). Therefore the therapeutic efficacy of the tamoxifen may not be compromised by the co-administration with red clover. Tamoxifen metabolism is primarily mediated by CYP2D6, CYP3A4 with minor contribution from CYP2C9, CYP2E1 and CYP1A2 isoforms. Although, red clover pre-treatment significantly (p < 0.05) decreased the mRNA expression and activity of CYP3a2, no effect on CYP2d4 and increased expression and activity of CYP2c11 could be the plausible reasons for lack of effect on tamoxifen and its metabolite pharmacokinetics in rats. CYP1a1 and CYP2b2 mRNA expression and activity were also significantly reduced by red clover. To extend the clinical utility of the present study, effect of red clover extract on major CYPs using human liver microsomes and HepG2 cell lines were also determined. Similar finding were observed in the human liver preparations as in rats.
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India.|Pharmacokinetics and Metabolism Division, CSIR- Central Drug Research Institute, Lucknow-226031, India.
authors.forename: Kanumuri Siva Rama
authors.initials: KS
authors.lastname: Raju
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India.|Pharmacokinetics and Metabolism Division, CSIR- Central Drug Research Institute, Lucknow-226031, India.
authors.forename: Isha
authors.initials: I
authors.lastname: Taneja
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India.|Pharmacokinetics and Metabolism Division, CSIR- Central Drug Research Institute, Lucknow-226031, India.
authors.forename: Guru Raghavendra
authors.initials: GR
authors.lastname: Valicherla
authors.affiliation: Analytical Chemistry Lab, CSIR-Indian Institute of Toxicology Research, Lucknow-226001, India.
authors.forename: Murali Krishna
authors.initials: MK
authors.lastname: Challagundla
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR- Central Drug Research Institute, Lucknow-226031, India.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR- Central Drug Research Institute, Lucknow-226031, India.
authors.forename: Anees Ahmed
authors.initials: AA
authors.lastname: Syed
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India.|Pharmacokinetics and Metabolism Division, CSIR- Central Drug Research Institute, Lucknow-226031, India.
authors.forename: Jiaur Rahman
authors.initials: JR
authors.lastname: Gayen
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raebareli-229010.
authors.forename: Sheelendra Pratap
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India.|Pharmacokinetics and Metabolism Division, CSIR- Central Drug Research Institute, Lucknow-226031, India.|Analytical Chemistry Lab, CSIR-Indian Institute of Toxicology Research, Lucknow-226001, India.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wahajuddin
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D005260:Female; D006207:Half-Life; D056945:Hep G2 Cells; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics*; D029921:Trifolium / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D020033:Protein Isoforms; D012333:RNA, Messenger; D013629:Tamoxifen; C016601:afimoxifene; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C025619:steroid 16-beta-hydroxylase