{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:25:59Z","timestamp":1789691159824,"version":"4.0.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pulmocide Ltd"},{"name":"Pulmocide Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Invasive fungal diseases (IFDs) cause high morbidity and mortality among immune-compromised patients. Triazoles, which are recommended to treat IFDs, inhibit and\/or are substrates for the phase 1 cytochrome P450 (CYP) pathway that metabolizes many drugs and frequently result in drug\u2013drug interactions (DDIs). Nebulized opelconazole is an investigational inhaled antifungal in development for the treatment of pulmonary aspergillosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro studies first assessed effects of opelconazole on CYP isoforms and human transporter protein interactions. Subsequently, a Phase 1 study in healthy volunteers assessed whether repeat daily dosing of inhaled opelconazole inhibited or induced CYP1A2 and CYP3A4 using the substrates caffeine and midazolam, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro analyses confirmed that opelconazole interactions with human CYPs were limited to competitive inhibition of CYP3A4 and weak induction potential for CYP3A4 and CYP1A2. These interactions occurred at concentrations higher than those expected at steady state following clinical dosing. Inhibition of a limited range of transporter proteins occurred at micromolar concentrations of opelconazole, but it was not found to be a substrate for carrier transporters. In the Phase 1 healthy volunteer study, inhaled opelconazole at steady state demonstrated no inhibition\/induction of CYP3A4 or CYP1A2 and was generally well tolerated. The Phase 1 study results confirmed that the potential for interactions of opelconazole with CYP3A4 and CYP1A2 substrates during concomitant use was negligible.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Systemic steady-state concentrations achieved after clinical dosing of inhaled opelconazole are unlikely to be associated with CYP-mediated DDIs or transporter-mediated DDIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf384","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T11:55:55Z","timestamp":1759406155000},"page":"3391-3400","source":"Crossref","is-referenced-by-count":6,"title":["<i>In vitro<\/i>\n                    and clinical data demonstrate negligible risk of drug\u2013drug interactions with opelconazole, a novel inhaled antifungal agent"],"prefix":"10.1093","volume":"80","author":[{"given":"Lindsey M R","family":"Cass","sequence":"first","affiliation":[{"name":"Pulmocide Ltd. , 44 Southampton Buildings, London WC2A 1AP ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ayrton","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd. , 44 Southampton Buildings, London WC2A 1AP ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-725X","authenticated-orcid":false,"given":"Roger J","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Antifungal Pharmacology Research Group, Radboud University Medical Centre , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Moore","sequence":"additional","affiliation":[{"name":"Pacific BioDevelopment, LLC , Davis, CA 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