{"doi":"10.3389/fphar.2022.918083","title":"Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, a Potential Oral Drug Candidate for COVID-19 Treatment","abstract":"Preclinical pharmacokinetics (PK) and In Vitro ADME properties of GS-441524, a potential oral agent for the treatment of Covid-19, were studied. GS-441524 was stable in vitro in liver microsomes, cytosols, and hepatocytes of mice, rats, monkeys, dogs, and humans. The plasma free fractions of GS-441524 were 62–78% across all studied species. The in vitro transporter study results showed that GS-441524 was a substrate of MDR1, BCRP, CNT3, ENT1, and ENT2; but not a substrate of CNT1, CNT2, and ENT4. GS-441524 had a low to moderate plasma clearance (CL p ), ranging from 4.1 mL/min/kg in dogs to 26 mL/min/kg in mice; the steady state volume distribution (Vd ss ) ranged from 0.9 L/kg in dogs to 2.4 L/kg in mice after IV administration. Urinary excretion appeared to be the major elimination process for GS-441524. Following oral administration, the oral bioavailability was 8.3% in monkeys, 33% in rats, 39% in mice, and 85% in dogs. The PK and ADME properties of GS-441524 support its further development as an oral drug candidate.","journal":"Frontiers in Pharmacology","year":2022,"id":248596,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":239787,"name":"Natalie R. Hagen","orcid":"0000-0002-1744-8632","position":1,"is_corresponding":false},{"id":288996,"name":"Elias Carvalho Padilha","orcid":"0000-0002-3794-9389","position":2,"is_corresponding":false},{"id":888048,"name":"Mengbi Yang","orcid":"0000-0001-6283-5829","position":3,"is_corresponding":false},{"id":288993,"name":"Pranav Shah","orcid":"0000-0003-0076-7159","position":4,"is_corresponding":false},{"id":227988,"name":"Catherine Z. Chen","orcid":"0000-0002-6900-6553","position":5,"is_corresponding":false},{"id":239792,"name":"Wenwei Huang","orcid":"0000-0002-7727-9287","position":6,"is_corresponding":false},{"id":326238,"name":"Pramod Terse","orcid":"0000-0002-3343-3342","position":7,"is_corresponding":false},{"id":558499,"name":"Philip E.J. Sanderson","orcid":null,"position":8,"is_corresponding":false},{"id":227992,"name":"Wei Zheng","orcid":"0000-0003-1034-0757","position":9,"is_corresponding":false},{"id":239790,"name":"Xin Xu","orcid":"0000-0003-1163-9304","position":10,"is_corresponding":false},{"id":288994,"name":"Amy Q. Wang","orcid":"0000-0001-7368-1917","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T00:24:14.794521Z","pmid":"36052127","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":[]}