{"doi":"10.1016/j.ejps.2014.04.004","title":"Inhibitory effects of p-aminohippurate and probenecid on the renal clearance of adefovir and benzylpenicillin as probe drugs for organic anion transporter (OAT) 1 and OAT3 in humans","abstract":null,"journal":"European Journal of Pharmaceutical Sciences","year":2014,"id":598947,"datarank":0.6814942173405006,"base_score":4.543294782270004,"endowment":4.543294782270004,"self_citation_contribution":0.6814942173405006,"citation_network_contribution":0.0,"self_endowment_contribution":0.6814942173405006,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":93,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":274530,"name":"Ying Tian","orcid":"0000-0001-7682-6907","position":1,"is_corresponding":false},{"id":1535082,"name":"Tomoe Fujita","orcid":null,"position":2,"is_corresponding":false},{"id":1535083,"name":"Yasuhiko Ikeda","orcid":null,"position":3,"is_corresponding":false},{"id":1535084,"name":"Yuji Kumagai","orcid":null,"position":4,"is_corresponding":false},{"id":1535086,"name":"Tsunenori Kondo","orcid":null,"position":5,"is_corresponding":false},{"id":1104915,"name":"Kazunari Tanabe","orcid":"0000-0003-1775-547X","position":6,"is_corresponding":false},{"id":1535088,"name":"Hideki Nakayama","orcid":null,"position":7,"is_corresponding":false},{"id":1535090,"name":"Shigeru Horita","orcid":null,"position":8,"is_corresponding":false},{"id":757306,"name":"Hiroyuki Kusuhara","orcid":"0000-0002-3641-8746","position":9,"is_corresponding":false},{"id":1535092,"name":"Yuichi Sugiyama","orcid":null,"position":10,"is_corresponding":false},{"id":1535081,"name":"Kazuya Maeda","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Inhibitory effects of p-aminohippurate and probenecid on the renal clearance of adefovir and benzylpenicillin as probe drugs for organic anion transporter (OAT) 1 and OAT3 in humans","abstract":"Probe substrates for, and inhibitors of, specific transporters are desired to evaluate quantitatively the in vivo functions of transporters in humans. Based on published data, adefovir and benzylpenicillin were selected as organic anion transporter (OAT) 1- and OAT3-selective probe substrates, respectively. In human kidney slices, probenecid potently inhibited the uptake of both adefovir and benzylpenicillin with inhibition constant (Ki) values of 18.6±5.1 and 12.6±4.2μM, respectively, whereas p-aminohippurate (PAH) preferentially inhibited adefovir uptake. A clinical drug-interaction study involving healthy subjects was performed to investigate the dose-dependent inhibition potencies of probenecid and PAH on the renal clearance of the probe substrates. Adefovir or benzylpenicillin was coadministered with different oral doses of probenecid (500, 750, or 1500mg) or intravenous PAH infusion rates (70, 120, or 210mg/min/person) to the same subject using a crossover design. The renal clearance of adefovir was reduced by 45% and 46% in the subjects treated with the maximum dose of probenecid and PAH, respectively, which was in accordance with the results of in vitro inhibition study. On the other hand, renal clearance of benzylpenicillin was reduced by 78% in the subjects treated with the maximum dose of probenecid (1500mg), which could be explained by its in vitro Ki values. However, PAH unexpectedly increased the renal clearance of benzylpenicillin by 47%. These results suggest that adefovir and benzylpenicillin can be used as probe drugs for OAT1 and OAT3, respectively, and that PAH can be used to investigate the role of OAT1 in the urinary excretion of drugs in humans, whereas it may modulate other transport processes in the kidney.","is_dataset_classified":null,"base_score":4.543294782270004,"endowment":4.543294782270004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24747579","pmcid":null,"openalex_id":"https://openalex.org/W2067808501","authors":[],"funders":[{"funder_name":"Ministry of Education, Culture, Sports, Science and Technology","grant_id":"","title":null},{"funder_name":"Japan Research Foundation for Clinical Pharmacology","grant_id":"","title":null}],"total_grants":2,"fwci":3.5886,"citation_percentile":0.94571108,"influential_citations":0,"citation_trend":[{"year":2015,"count":4},{"year":2016,"count":10},{"year":2017,"count":12},{"year":2018,"count":9},{"year":2019,"count":13},{"year":2020,"count":6},{"year":2021,"count":8},{"year":2022,"count":9},{"year":2023,"count":6},{"year":2024,"count":10},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0928098714001560?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0928098714001560?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ejps.2014.04.004","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24747579","host_type":"repository"}],"fields_of_study":["Drug Transport and Resistance Mechanisms","Pharmacological Effects and Toxicity Studies","Pregnancy and Medication Impact"],"mesh_terms":["Adenine","Adult","Drug Interactions","Humans","Kidney","Male","p-Aminohippuric Acid","Penicillin G","Probenecid","Organic Anion Transport Protein 1","Organic Anion Transporters, Sodium-Independent","Young Adult","HEK293 Cells","Organophosphonates","In Vitro Techniques"],"keywords":["Probenecid","Organic anion transporter 1","Chemistry","Adefovir","Pharmacology","Benzylpenicillin","Transporter","In vivo","In vitro","Renal function","Biochemistry","Biology","Antibiotics","Immunology","Renal Clearance","Organic Anion Transporter (Oat)","Probe Drug"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T16:28:06.316075Z","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":[]}