{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:38:59Z","timestamp":1759941539457},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T00:00:00Z","timestamp":1474848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Moberg Pharma"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (<jats:styled-content style=\"fixed-case\">HNC<\/jats:styled-content>) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 <jats:styled-content style=\"fixed-case\">HNC<\/jats:styled-content> patients with oral mucositis and as multiple doses to five patients with <jats:styled-content style=\"fixed-case\">HNC<\/jats:styled-content>. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with <jats:styled-content style=\"fixed-case\">HNC<\/jats:styled-content>, respectively, after administration. The plasma concentration\u2013time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed\u2010effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) of bupivacaine lozenge was best described by a two\u2010compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000\u20132250 ng\/ml) which have caused toxic symptoms. The <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> model suggested that relative bioavailability was two times higher in <jats:styled-content style=\"fixed-case\">HNC<\/jats:styled-content> patients with oral mucositis grade 1\u20132 and three times higher in <jats:styled-content style=\"fixed-case\">HNC<\/jats:styled-content> patients with oral mucositis grade 3\u20134 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25\u2010mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit.<\/jats:p>","DOI":"10.1111\/bcpt.12644","type":"journal-article","created":{"date-parts":[[2016,7,19]],"date-time":"2016-07-19T06:53:05Z","timestamp":1468911185000},"page":"71-78","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis"],"prefix":"10.1111","volume":"120","author":[{"given":"Stine","family":"Mogensen","sequence":"first","affiliation":[{"name":"Clinical Research Centre Copenhagen University Hospital Hvidovre Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Sverrisd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Department 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