{"doi":"10.1007/s40261-016-0476-x","title":"Pharmacokinetics, Pharmacodynamics, and Safety of Entospletinib, a Novel pSYK Inhibitor, Following Single and Multiple Oral Dosing in Healthy Volunteers","abstract":null,"journal":"Clinical Drug Investigation","year":2017,"id":613382,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"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":1580204,"name":"Julie A. Di Paolo","orcid":null,"position":1,"is_corresponding":false},{"id":827264,"name":"Feng Jin","orcid":"0000-0002-9099-9318","position":2,"is_corresponding":false},{"id":1580205,"name":"Lixin Shao","orcid":null,"position":3,"is_corresponding":false},{"id":601049,"name":"Shringi Sharma","orcid":"0000-0002-3120-225X","position":4,"is_corresponding":false},{"id":1580206,"name":"Michelle Robeson","orcid":null,"position":5,"is_corresponding":false},{"id":595639,"name":"Brian P. Kearney","orcid":null,"position":6,"is_corresponding":false},{"id":1580203,"name":"Srini Ramanathan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Pharmacokinetics, Pharmacodynamics, and Safety of Entospletinib, a Novel pSYK Inhibitor, Following Single and Multiple Oral Dosing in Healthy Volunteers","abstract":"BACKGROUND AND OBJECTIVES: Entospletinib is a selective, reversible, adenosine triphosphate-competitive small-molecule spleen tyrosine kinase (SYK) inhibitor that blocks B cell receptor-mediated signaling and proliferation in B lymphocytes. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of entospletinib in a double-blind, single/multiple ascending dose study in healthy volunteers. METHODS: In sequential cohorts, 120 subjects received entospletinib (25-1200 mg; fasted) as single or twice-daily oral doses for 7 days. Along with pharmacokinetics, the study assessed functional inhibition of ex vivo anti-immunoglobulin E-stimulated CD63 expression on basophils and pervanadate-evoked phosphorylated SYK (pSYK) Y525. Safety and tolerability were assessed throughout the study. RESULTS: Entospletinib was generally well-tolerated over a 48-fold dose range. Adverse events (AEs) were generally mild to moderate, with no AE-driven study drug discontinuations noted. Entospletinib displayed a median plasma half-life of 9-15 h; entospletinib exposures reached a plateau at ≥600 mg twice daily (likely due to solubility-limited absorption) and provided >90% CD63 inhibition at peak concentrations and >60% inhibition at trough concentrations (corresponding pSYK inhibition of >70 and >50%). CONCLUSION: The overall safety, pharmacokinetics, and pharmacodynamics profiles of entospletinib support further clinical evaluation.","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27785737","pmcid":null,"openalex_id":"https://openalex.org/W2546247047","authors":[],"funders":[],"total_grants":0,"fwci":0.5638,"citation_percentile":0.67495826,"influential_citations":0,"citation_trend":[{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":7},{"year":2022,"count":4},{"year":2023,"count":6},{"year":2024,"count":2},{"year":2025,"count":2}],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007%2Fs40261-016-0476-x.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007%2Fs40261-016-0476-x.pdf","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1007/s40261-016-0476-x.pdf","host_type":"publisher"},{"url":"http://link.springer.com/article/10.1007/s40261-016-0476-x/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s40261-016-0476-x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27785737","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5250654","host_type":"repository"}],"fields_of_study":["Mast cells and histamine","PI3K/AKT/mTOR signaling in cancer","Inflammatory Bowel Disease","Adolescent","Adult","B-Lymphocytes","Basophils","Cohort Studies","Dose-Response Relationship, Drug","Double-Blind Method","Female","Food-Drug Interactions","Healthy Volunteers","Humans","Male","Middle Aged","Syk Kinase","Tetraspanin 30","Vanadates","Young Adult"],"mesh_terms":["Syk Kinase","Adolescent","Adult","B-Lymphocytes","Basophils","Dose-Response Relationship, Drug","Double-Blind Method","Female","Humans","Male","Middle Aged","Vanadates","Cohort Studies","Food-Drug Interactions","Young Adult","Tetraspanin 30","Healthy Volunteers"],"keywords":["Pharmacokinetics","Pharmacodynamics","Pharmacology","Medicine","Tolerability","Adverse effect","Syk","Safety pharmacology","Dosing","Drug","Internal medicine","Receptor","Tyrosine kinase"],"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":"2026-08-02T07:55:10.329796Z","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":[]}