{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:36:21Z","timestamp":1760452581472},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,3,24]],"date-time":"2014-03-24T00:00:00Z","timestamp":1395619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Sirolimus (rapamycin) is a mammalian target of rapamycin (<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>) inhibitor with antiproliferative activity. Its systemic administration is currently evaluated for the management of squamous cell carcinoma and various oral disorders. Topical oral application can enhance availability, efficacy and improve safety and compliance. Our objective was to evaluate the release profile and the safety of a sirolimus mouthwash.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and methods<\/jats:title><jats:p>A sirolimus mouthwash (0.05\u00a0mg\u00a0ml<jats:sup>\u22121<\/jats:sup>) was applied to ten healthy male volunteers. Saliva and blood samples were taken after rinsing. Mass spectrometry and chemiluminescent microparticle immunoassay were used to determine saliva and blood levels of sirolimus. A topical oral release profile measurement and safety evaluation were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After rinsing with the mouthwash, a classic immediate release profile was noted in the oral cavity. Extremely high initial sirolimus levels rapidly declined over a 4\u2010hour period. Systemic exposure was limited, with a maximum level significantly lower than therapeutic doses, and safety was confirmed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A single rinse with sirolimus mouthwash leads to high transient levels of the drug in the saliva. Although levels were variable, a therapeutic concentration was achieved topically along with minimal systemic absorption. These results broaden the potential clinical use of oral topical rapalogs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.12229","type":"journal-article","created":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T13:15:04Z","timestamp":1392729304000},"page":"768-772","source":"Crossref","is-referenced-by-count":9,"title":["Levels of sirolimus in saliva and blood following mouthwash application"],"prefix":"10.1111","volume":"20","author":[{"given":"Z","family":"Nudelman","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics Faculty of Medicine The Institute for Drug Research School of Pharmacy The Hebrew University Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Faculty of Medicine The Institute for Drug Research School of Pharmacy The Hebrew University Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Barasch","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Faculty of Medicine The Institute for Drug Research School of Pharmacy The Hebrew University Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Nemirovski","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Faculty of Medicine The Institute for Drug Research School of Pharmacy The Hebrew University Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Findler","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine Hebrew University\u2010Hadassah School of Dental Medicine Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Pikovsky","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine Hebrew University\u2010Hadassah School of Dental Medicine Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JS","family":"Gutkind","sequence":"additional","affiliation":[{"name":"Oral and Pharyngeal Cancer Branch National Institute of Craniofacial and Dental Research NIH Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Czerninski","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine Hebrew University\u2010Hadassah School of Dental Medicine Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24351"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.5005\/jcdp-9-3-72"},{"key":"e_1_2_7_4_1","first-page":"629","article-title":"Long\u2010term patient benefit with biodegradable polymer biolimus eluting stent","volume":"60","author":"Corti 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