{"doi":"10.17615/71s9-mb98","title":"Multidrug Resistance-Associated Protein 2 Is Primarily Responsible for the Biliary Excretion of Fexofenadine in Mice","abstract":"Previous studies implicated P-glycoprotein (P-gp) as the major transport protein responsible for the biliary excretion of fexofenadine (FEX). However, FEX biliary excretion was not impaired in P-gp- or Bcrp-knockout mice, and Mrp2-deficient rats. The present study tested the hypothesis that species differences exist in the transport protein primarily responsible for FEX biliary excretion between mice and rats. Livers from Mrp2-knockout (Mrp2KO) mice and Mrp2-deficient (TR−) rats were perfused in a single-pass manner with 0.5 μM FEX. GF120918 (10 μM) was employed to inhibit P-gp and Bcrp. The biliary excretion rate of FEX was decreased 85% in Mrp2KO relative to wild-type mice (18.4 ± 2.2 vs. 122 ± 34 pmol/min/g liver). In mice, more than 50% of FEX unbound intrinsic biliary clearance (CLbile, int = 3.0 ml/hr/g liver) could be attributed to Mrp2 (Mrp2-dependent CLbile, int ~ 1.7 ml/hr/g liver), with P-gp and Bcrp playing a minor role (P-gp- and Bcrp-dependent CLbile, int ~ 0.3 ml/hr/g liver). Approximately one-third of FEX CLbile, int was attributed to unidentified mechanisms in mice. In contrast to mice, FEX biliary excretion rate (245 ± 38 and 250 ± 25 pmol/min/g liver) and CLbile, int (9.72 ± 2.5 and 6.49 ± 0.68 ml/hr/g liver) were comparable between Mrp2-deficient (TR−) and control Wistar rats, respectively, suggesting that unidentified transport mechanism(s) can completely compensate for the loss of Mrp2 function in rats. Mrp2 clearly plays a major role in FEX biliary excretion in mice. In conclusion, remarkable species differences exist in FEX hepatobiliary transport mechanisms.","journal":"UNC Libraries","year":2020,"id":142602,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":548112,"name":"N. J. Patel","orcid":null,"position":1,"is_corresponding":false},{"id":594807,"name":"Maciej J. Zamek‐Gliszczynski","orcid":"0000-0002-6685-1006","position":2,"is_corresponding":false},{"id":594806,"name":"Xiaojin Tian","orcid":"0009-0006-3774-0813","position":3,"is_corresponding":false},{"id":544853,"name":"T. J. Raub","orcid":null,"position":4,"is_corresponding":false},{"id":26336,"name":"J. Li","orcid":"0009-0000-5782-8050","position":5,"is_corresponding":false},{"id":597142,"name":"K.-i. Nezasa","orcid":null,"position":6,"is_corresponding":false},{"id":407251,"name":"Kim L. R. Brouwer","orcid":"0000-0003-1945-4929","position":7,"is_corresponding":false},{"id":532352,"name":"A. S. Bridges","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:31.424593Z","pmid":null,"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":[]}