{"doi":"10.1211/0022357001773670","title":"Oral, Intraperitoneal and Intravenous Pharmacokinetics of Deramciclane and its <i>N</i>-desmethyl Metabolite in the Rat","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The pharmacokinetic properties of deramciclane fumarate (EGIS-3886), a new potential anxiolitic agent, and its N-desmethyl metabolite have been investigated in Wistar rats after 10 mg kg−1 deramciclane fumarate was administered orally, intraperitoneally or intravenously.</jats:p>\n               <jats:p>A highly sensitive, validated and optimized gas chromatographic method with nitrogen selective detection (GC-NPD) using a solid-phase extraction technique was used to determine plasma levels of the parent compound and its N-desmethyl metabolite.</jats:p>\n               <jats:p>After oral administration the absorption of the parent compound was very fast (tmax 0.5 h). The maximum plasma concentration (Cmax) was detected at 44.9, ≥177.8 and ≥2643.0 ng mL−1 after oral, intraperitoneal and intravenous administration of deramciclane, respectively. For the metabolite the respective Cmax values were 32.0, ≥25.4 and 51.0 ng mL−1. The pharmacokinetic curves of both the parent compound and its metabolite showed enterohepatic recirculation for all administration routes. The biological half-life (tβ1/2) for deramciclane ranged from 3.42 to 5.44 h and for the N-desmethyl metabolite the range was 2.90–5.44 h, after administration of the drug by the three different routes. After intravenous administration AUC0-∞ of deramciclane was 29.2- and 5.4-times higher than that observed after oral and intraperitoneal treatment, respectively. These AUC0-∞ ratios were only 2.1- and 1.5-times higher for the metabolite. The absolute bioavailability of deramciclane in rats was 3.42% after oral and 18.49% after intraperitoneal administration.</jats:p>\n               <jats:p>The comparative pharmacokinetic study of deramciclane in rat after the different administration routes showed fast absorption. Furthermore, plasma levels were found to be administration route-dependent, low bioavailability of the parent compound indicated an extremely fast and strong first-pass metabolism. The apparent volume of distribution suggested strong tissue binding after administration of the drug by any of the three routes studied.</jats:p>","journal":"Journal of Pharmacy and Pharmacology","year":2000,"id":41147,"datarank":1.3354535115595558,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.8356228350332752,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.8356228350332752,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":21,"citers_with_citation_signal":17,"citers_with_endowment":17,"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":198656,"name":"Miklós Abermann","orcid":null,"position":1,"is_corresponding":false},{"id":198657,"name":"Erzsébet Bojti","orcid":null,"position":2,"is_corresponding":false},{"id":198658,"name":"Gyula Grézal","orcid":null,"position":3,"is_corresponding":false},{"id":198659,"name":"Samar Al-Behaisi","orcid":null,"position":4,"is_corresponding":false},{"id":198660,"name":"Imre Klebovich","orcid":null,"position":5,"is_corresponding":false},{"id":198655,"name":"Katalin Balogh Nemes","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10716602","pmcid":null,"openalex_id":"https://openalex.org/W2056938528","authors":[],"funders":[],"total_grants":0,"fwci":0.641,"citation_percentile":0.70102314,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2016,"count":2},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2022,"count":2},{"year":2023,"count":2},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"bronze","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://academic.oup.com/jpp/article-pdf/52/1/47/36784345/0022357001773670.pdf","host_type":"journal"},{"url":"https://academic.oup.com/jpp/article-pdf/52/1/47/36784345/0022357001773670.pdf","host_type":"BRONZE"},{"url":"https://academic.oup.com/jpp/article-pdf/52/1/47/36784345/0022357001773670.pdf","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1211%2F0022357001773670","host_type":"publisher"},{"url":"https://academic.oup.com/jpp/article-pdf/52/1/47/60263302/0022357001773670.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1211/0022357001773670","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10716602","host_type":"repository"}],"fields_of_study":["Cancer Treatment and Pharmacology","HIV/AIDS drug development and treatment","Pharmacogenetics and Drug Metabolism","Medicine","Chemistry","Administration, Oral","Animals","Anti-Anxiety Agents","Area Under Curve","Biological Availability","Camphanes","Half-Life","Injections, Intraperitoneal","Injections, Intravenous","Male","Molecular Structure","Rats","Rats, Wistar"],"mesh_terms":["Administration, Oral","Animals","Biological Availability","Camphanes","Half-Life","Injections, Intraperitoneal","Injections, Intravenous","Male","Anti-Anxiety Agents","Molecular Structure","Rats, Wistar","Area Under Curve","Rats"],"keywords":["Metabolite","Pharmacokinetics","Desmethyl","Cmax","Pharmacology","Bioavailability","Oral administration","Chemistry","Active metabolite","Absorption (acoustics)","Chromatography","Medicine","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-12T21:41:38.853025Z","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":[]}