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Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  • Stine Mogensen
  • Eva Sverrisdóttir
  • Kolbrún Sveinsdóttir
  • Charlotte Treldal
  • Kenneth Jensen
  • Anders Bonde Jensen
  • Claus Andrup Kristensen
  • Jette Jacobsen
  • Mads Kreilgaard
  • Janne Petersen
  • Ove Andersen
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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 (HNC) patients with oral mucositis. A lozenge containing 5 mg, 10 mg, 25 mg and 50mg bupivacaine, respectively, was administered as single dose to 10 healthy invididuals and lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to 5 HNC patients. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the HNC patients, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using non-linear mixed effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All observed plasma concentrations were well below bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was 2-fold higher in HNC patients with oral mucositis grade 1-2, and 3-fold higher in HNC patients with oral mucositis grade 3-4 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 5 days. The 25 mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every 2 hr for 16 hr a day, the lozengscan be administered with minimum risk of exceeding the toxic limit. This article is protected by copyright. All rights reserved.

TidsskriftBasic & clinical pharmacology & toxicology
Udgave nummer1
Sider (fra-til)71-78
StatusUdgivet - jan. 2017

ID: 48263469