{"doi":"10.3390/pharmaceutics14091933","title":"A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug–Drug Interaction Liabilities","abstract":"In recent years, various endogenous compounds have been proposed as putative biomarkers for the hepatic uptake transporters OATP1B1 and OATP1B3 that have the potential to predict transporter-mediated drug-drug interactions (DDIs). However, these compounds have often been identified from top-down strategies and have not been fully utilized as a substitute for traditional DDI studies. In an attempt to eliminate observer bias in biomarker selection, we applied a bottom-up, untargeted metabolomics screening approach in mice and found that plasma levels of the conjugated bile acid chenodeoxycholate-24-glucuronide (CDCA-24G) are particularly sensitive to deletion of the orthologous murine transporter Oatp1b2 (31-fold increase vs. wild type) or the entire Oatp1a/1b(-/-)cluster (83-fold increased), whereas the humanized transgenic overexpression of hepatic OATP1B1 or OATP1B3 resulted in the partial restoration of transport function. Validation studies with the OATP1B1/OATP1B3 inhibitors rifampin and paclitaxel in vitro as well as in mice and human subjects confirmed that CDCA-24G is a sensitive and rapid response biomarker to dose-dependent transporter inhibition. Collectively, our study confirmed the ability of CDCA-24G to serve as a sensitive and selective endogenous biomarker of OATP1B-type transport function and suggests a template for the future development of biomarkers for other clinically important xenobiotic transporters.","journal":"Pharmaceutics","year":2022,"id":282691,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":570273,"name":"Yan Jin","orcid":"0000-0002-4124-3362","position":1,"is_corresponding":false},{"id":922540,"name":"Hanieh Taheri","orcid":"0000-0003-3236-7870","position":2,"is_corresponding":false},{"id":370005,"name":"Keith T. Schmidt","orcid":"0009-0008-0285-0216","position":3,"is_corresponding":false},{"id":310490,"name":"Alice A. Gibson","orcid":"0000-0001-5910-5067","position":4,"is_corresponding":false},{"id":958680,"name":"Stefan A.J. Buck","orcid":"0000-0003-1367-8403","position":5,"is_corresponding":false},{"id":310489,"name":"Eric D. Eisenmann","orcid":"0000-0003-1176-675X","position":6,"is_corresponding":false},{"id":958681,"name":"Ron H.J. Mathijssen","orcid":"0000-0001-5667-5697","position":7,"is_corresponding":false},{"id":109200,"name":"William D. Figg","orcid":"0000-0003-2428-5613","position":8,"is_corresponding":false},{"id":342107,"name":"Sharyn D. Baker","orcid":"0000-0003-3062-3252","position":9,"is_corresponding":false},{"id":255308,"name":"Alex Sparreboom","orcid":"0000-0003-2660-6644","position":10,"is_corresponding":false},{"id":255307,"name":"Shuiying Hu","orcid":"0000-0002-9806-7734","position":11,"is_corresponding":false},{"id":310491,"name":"Yang Li","orcid":"0000-0001-9055-2332","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T00:29:19.691592Z","pmid":"36145680","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}