Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis
| Autor: | Jette Bredahl Jacobsen, Janne Petersen, Eva Sverrisdóttir, Ove Andersen, Mads Kreilgaard, Kolbrún Sveinsdottir, Claus A. Kristensen, Kenneth Jensen, Stine Mogensen, Anders Bonde Jensen, Charlotte Treldal |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Mucositis Metabolic Clearance Rate Biological Availability Pain Absorption (skin) Toxicology Models Biological Oral Mucosal Absorption Severity of Illness Index 030226 pharmacology & pharmacy Drug Administration Schedule Intestinal absorption 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Administration Mucosal Humans Anesthetics Local Radiation Injuries Pharmacology Bupivacaine Dose-Response Relationship Drug business.industry Mouth Mucosa General Medicine medicine.disease Bioavailability Dose–response relationship Intestinal Absorption Head and Neck Neoplasms 030220 oncology & carcinogenesis Anesthesia Female business Lozenge medicine.drug |
| Zdroj: | Mogensen, S, Sverrisdóttir, E, Sveinsdóttir, K, Treldal, C, Jensen, K, Jensen, A B, Kristensen, C A, Jacobsen, J, Kreilgaard, M, Petersen, J & Andersen, O 2017, ' Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis ', Basic & Clinical Pharmacology & Toxicology, vol. 120, no. 1, pp. 71-78 . https://doi.org/10.1111/bcpt.12644 |
| ISSN: | 1742-7835 |
| DOI: | 10.1111/bcpt.12644 |
| Popis: | 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, 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 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear 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 the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times 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 five 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 two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. |
| Databáze: | OpenAIRE |
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