{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:51:02Z","timestamp":1791546662786,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:00:00Z","timestamp":1608336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    PC945 is a novel antifungal triazole formulated for nebulized delivery to treat lung\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    infections. Pharmacokinetic and safety profiles from nonclinical studies and clinical trials in healthy subjects, and subjects with mild asthma were characterized. Toxicokinetics were assessed following daily 2\u2010hour inhalation for 14\u00a0days. Potential for drug\u2010drug interactions was evaluated using pooled human liver microsomes. Clinical safety and pharmacokinetics were assessed following (a) single inhaled doses (0.5\u201010\u00a0mg), (b) 7\u2010day repeat doses (5\u00a0mg daily) in healthy subjects; (c) a single dose (5\u00a0mg) in subjects with mild asthma.\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    occurred 4\u00a0hours (rats) or immediately (dogs) after a single dose. PC945 lung concentrations were substantially higher (&gt;2000\u2010fold) than those in plasma. PC945 only inhibited CYP3A4\/5 substrate metabolism (IC\n                    <jats:sub>50<\/jats:sub>\n                    : 1.33\u00a0\u00b5M [testosterone] and 0.085\u00a0\u00b5M [midazolam]). Geometric mean\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    was 322\u00a0pg\/mL (healthy subjects) and 335\u00a0pg\/mL (subjects with mild asthma) 4\u20105\u00a0hours (median t\n                    <jats:sub>max<\/jats:sub>\n                    ) after a single inhalation (5\u00a0mg). Following repeat, once daily inhalation (5\u00a0mg), Day 7\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    was 951\u00a0pg\/mL (0.0016\u00a0\u00b5M) 45\u00a0minutes after dosing. Increases in\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u201324h<\/jats:sub>\n                    were approximately dose\u2010proportional (0.5\u201010\u00a0mg). PC945 administration was well tolerated in both healthy subjects and subjects with mild asthma. Treatment\u2010emergent adverse events were mild\/moderate and resolved before the study ended. No clinically significant lung function changes were observed. PC945 pharmacokinetics translated from nonclinical species to humans showed slow absorption from lungs and low systemic exposure, thereby limiting the potential for adverse side effects and drug interactions commonly seen with systemically delivered azoles.\n                  <\/jats:p>","DOI":"10.1002\/prp2.690","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T07:12:58Z","timestamp":1608361978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3719-0883","authenticated-orcid":false,"given":"Lindsey","family":"Cass","sequence":"first","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Murray","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Davis","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Woodward","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"Albayaty","sequence":"additional","affiliation":[{"name":"Parexel Early Phase Clinical Unit Level 7 Northwick Park Hospital Harrow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pete","family":"Strong","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ayrton","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Brindley","sequence":"additional","affiliation":[{"name":"KinetAssist Limited Quothquan UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne","family":"Prosser","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Murray","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"French","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Haywood","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Wallis","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth","family":"Rapeport","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.2017160110"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30316-X"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206291"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00055-08"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2008-740ST"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2016.12.71"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/598327"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250903463878"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15270"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/11594090-000000000-00000"},{"key":"e_1_2_11_12_1","unstructured":"SunoseM ColleyTC ItoK RapeportG StrongP. 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