ArticleCancer prevention research (Philadelphia, Pa.)2013
Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo.
Article in Cancer prevention research (Philadelphia, Pa.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Dexamethasone-Mediated Regulation of CYP3A4 and UGTs in Human Hepatoma HuH-7 Cells.Fundamental & clinical pharmacology · 2026Article
- Advancing Predictions of Oral Drug Absorption, CYP3A4 Induction, and Transporter-Mediated Interactions Using a Human Primary Intestinal 3D Model (EpiIntestinal™).Clinical pharmacology and therapeutics · 2025Article
- Estrogen Receptors as Key Factors in Carcinogenesis.Biomedicines · 2025Review
- Treating ER-positive breast cancer: a review of the current FDA-approved SERMs and SERDs and their mechanisms of action.Oncology reviews · 2025Review
- Efflux and uptake transport and gut microbial reactivation of raloxifene glucuronides.Basic & clinical pharmacology & toxicology · 2025Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Epigenetics in drug disposition & drug therapy: symposium report of the 24Drug metabolism reviews · 2022Review
- Article
- Racial Disparity in Drug Disposition in the Digestive Tract.International journal of molecular sciences · 2021Review
- The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates.Frontiers in pharmacology · 2021Review
- Characterization of metabolic activity, isozyme contribution and species differences of bavachin, and identification of efflux transporters for bavachin-O-glucuronide in HeLa1A1 cells.The Journal of pharmacy and pharmacology · 2020Article
- Pharmacogenomics Study for Raloxifene in Postmenopausal Female with Osteoporosis.Disease markers · 2020Article
- Effect of CYP2C19, UGT1A8, and UGT2B7 on valproic acid clearance in children with epilepsy: a population pharmacokinetic model.European journal of clinical pharmacology · 2018Article
- Label-free LC-MS/MS shotgun proteomics to investigate the anti-inflammatory effect of rCC16.Molecular medicine reports · 2016Article
- Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines.The Journal of pharmacology and experimental therapeutics · 2016Article
- Quantitative prediction and clinical evaluation of an unexplored herb-drug interaction mechanism in healthy volunteers.CPT: pharmacometrics & systems pharmacology · 2015Article
- Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- MicroRNA regulation of the major drug-metabolizing enzymes and related transcription factors.Drug metabolism reviews · 2015Review
- Triple Recycling Processes Impact Systemic and Local Bioavailability of Orally Administered Flavonoids.The AAPS journal · 2015Article
- Identification of diet-derived constituents as potent inhibitors of intestinal glucuronidation.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Raloxifene is a second-generation selective estrogen receptor modulator used for the prevention and treatment of osteoporosis and the prevention of breast cancer in postmenopausal women. Raloxifene is extensively metabolized by glucuronidation to form raloxifene-6-glucuronide (ral-6-Gluc) and raloxifene-4'-glucuronide (ral-4'-Gluc). The goal of the present study was to determine whether functional polymorphisms in active UGTs could play a role in altered raloxifene glucuronidation in vivo. Using homogenates from HEK293 UGT-overexpressing cell lines, raloxifene was shown to be glucuronidated primarily by the hepatic UGTs 1A1 and 1A9 and the extra-hepatic UGTs 1A8 and 1A10; no detectable raloxifene glucuronidation activity was found for UGT2B enzymes. Functional UGT1A1 transcriptional promoter genotypes were significantly (Ptrend = 0.005) associated with ral-6-Gluc formation in human liver microsomes, and, consistent with the decreased raloxifene glucuronidation activities observed in vitro with cell lines overexpressing UGT1A8 variants, the UGT1A8*2 variant was significantly (P = 0.023) correlated with total raloxifene glucuronide formation in human jejunum homogenates. While ral-4'-Gluc exhibited 1:100th the anti-estrogenic activity of raloxifene itself as measured by binding to the estrogen receptor, raloxifene glucuronides comprised about 99% of the circulating raloxifene dose in raloxifene-treated subjects, with ral-4'-Gluc comprising ~70% of raloxifene glucuronides. Plasma ral-6-Gluc (Ptrend = 0.0025), ral-4'-Gluc (Ptrend = 0.001), and total raloxifene glucuronides (Ptrend = 0.001) were increased in raloxifene-treated subjects who were predicted slow metabolizers [UGT1A8 (*1/*3)] versus intermediate metabolizers [UGT1A8 (*1/*1) or UGT1A8 (*1/*2)] versus fast metabolizers [UGT1A8 (*2/*2). These data suggest that raloxifene metabolism may be dependent on UGT1A8 genotype and that UGT1A8 genotype may play an important role in overall response to raloxifene.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.