{"doi":"10.1089/jop.2020.0137","title":"Pharmacological Profile and Ocular Hypotensive Effects of Cromakalim Prodrug 1, a Novel ATP-Sensitive Potassium Channel Opener, in Normotensive Dogs and Nonhuman Primates","abstract":"Purpose: To evaluate pharmacokinetic parameters and ocular hypotensive effects of cromakalim prodrug 1 (CKLP1) in normotensive large animal models. Methods: Optimal CKLP1 concentration was determined by dose response and utilized in short- (5–8 days) and long-term (60 days) evaluation in hound dogs ( n = 5) and African Green Monkeys ( n = 5). Blood pressure was recorded 3–5 times per week with a tail cuff. Concentrations of CKLP1 and the parent compound levcromakalim were assessed in hound dog plasma and select tissues by LC-MS/MS after bilateral ocular treatment with CKLP1 for 8 days. Pharmacokinetic parameters were calculated from days 1, 4, and 8 data. After necropsy, histology was assessed in 43 tissue samples from each animal. Results: In hound dogs and African Green monkeys, 10 mM CKLP1 (optimal concentration) significantly lowered intraocular pressure (IOP) by 18.9% ± 1.1% and 16.7% ± 6.7%, respectively, compared with control eyes ( P < 0.05). During treatment, no significant change in systolic or diastolic blood pressure was observed in either species ( P > 0.1). Average values for half-life of CKLP1 was 295.3 ± 140.4 min, C max, 10.5 ± 1.6 ng/mL, and area under the concentration vs. time curve (AUC last ) 5261.4 ± 918.9 ng·min/mL. For levcromakalim, average values of half-life were 96.2 ± 27 min, C max 1.2 ± 0.2 ng/mL, and AUC last 281.2 ± 110.8 ng·min/mL. No significant pathology was identified. Conclusions: CKLP1 lowered IOP in hound dogs and African green monkeys with no effect on systemic blood pressure. Ocular topical treatment of CKLP1 showed excellent tolerability even after extended treatment periods.","journal":"Journal of Ocular Pharmacology and Therapeutics","year":2021,"id":189852,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232648,"name":"Rachel A. Kudgus","orcid":"0009-0003-3074-7682","position":1,"is_corresponding":false},{"id":753989,"name":"Bradley H. Holman","orcid":null,"position":2,"is_corresponding":false},{"id":753222,"name":"Tommy A. Rinkoski","orcid":"0000-0001-8122-8215","position":3,"is_corresponding":false},{"id":753990,"name":"Cheryl R. Hann","orcid":null,"position":4,"is_corresponding":false},{"id":753991,"name":"Cindy K. Bahler","orcid":null,"position":5,"is_corresponding":false},{"id":753992,"name":"Eric McCloud","orcid":null,"position":6,"is_corresponding":false},{"id":459785,"name":"Susan E. Appt","orcid":"0000-0003-4953-2940","position":7,"is_corresponding":false},{"id":232647,"name":"Joel M. Reid","orcid":"0000-0003-2872-3123","position":8,"is_corresponding":false},{"id":387857,"name":"Peter I. Dosa","orcid":"0000-0002-0081-3867","position":9,"is_corresponding":false},{"id":528702,"name":"Michael P. Fautsch","orcid":"0000-0002-9115-2485","position":10,"is_corresponding":false},{"id":753988,"name":"Uttio Roy Chowdhury","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:49:22.671571Z","pmid":"33784195","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":[]}