{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:52:34Z","timestamp":1777909954091,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To evaluate pharmacokinetic parameters and ocular hypotensive effects of cromakalim prodrug 1 (CKLP1) in normotensive large animal models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Optimal CKLP1 concentration was determined by dose response and utilized in short- (5\u20138 days) and long-term (60 days) evaluation in hound dogs (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20095) and African Green Monkeys (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20095). Blood pressure was recorded 3\u20135 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In hound dogs and African Green monkeys, 10\u2009mM CKLP1 (optimal concentration) significantly lowered intraocular pressure (IOP) by 18.9%\u2009\u00b1\u20091.1% and 16.7%\u2009\u00b1\u20096.7%, respectively, compared with control eyes (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u20090.05). During treatment, no significant change in systolic or diastolic blood pressure was observed in either species (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&gt;\u20090.1). Average values for half-life of CKLP1 was 295.3\u2009\u00b1\u2009140.4\u2009min, C\n                      <jats:sub>max,<\/jats:sub>\n                      10.5\u2009\u00b1\u20091.6\u2009ng\/mL, and area under the concentration vs. time curve (AUC\n                      <jats:sub>last<\/jats:sub>\n                      ) 5261.4\u2009\u00b1\u2009918.9\u2009ng\u00b7min\/mL. For levcromakalim, average values of half-life were 96.2\u2009\u00b1\u200927\u2009min, C\n                      <jats:sub>max<\/jats:sub>\n                      1.2\u2009\u00b1\u20090.2\u2009ng\/mL, and AUC\n                      <jats:sub>last<\/jats:sub>\n                      281.2\u2009\u00b1\u2009110.8\u2009ng\u00b7min\/mL. No significant pathology was identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2020.0137","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T16:55:27Z","timestamp":1617123327000},"page":"251-260","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Pharmacological Profile and Ocular Hypotensive Effects of Cromakalim Prodrug 1, a Novel ATP-Sensitive Potassium Channel Opener, in Normotensive Dogs and Nonhuman Primates"],"prefix":"10.1177","volume":"37","author":[{"given":"Uttio","family":"Roy Chowdhury","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A.","family":"Kudgus","sequence":"additional","affiliation":[{"name":"Department of Oncology Research, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley H.","family":"Holman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommy A.","family":"Rinkoski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl R.","family":"Hann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy K.","family":"Bahler","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"McCloud","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Appt","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel M.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Oncology Research, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter I.","family":"Dosa","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Fautsch","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16257-0"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00061198-200312000-00004"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/108076802760116205"},{"key":"e_1_3_5_6_2","doi-asserted-by":"crossref","first-page":"460483","DOI":"10.1155\/2014\/460483","article-title":"The effects of topical antiglaucoma drugs as monotherapy on the ocular surface: A prospective study","volume":"2014","author":"Aydin Kurna S.","year":"2014","unstructured":"Aydin Kurna S., , Acikgoz S., , Altun A., , Ozbay N., , Sengor T., , and Olcaysu O.O. 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