• Mona Darwish, Mary Kirby, Philmore Robertson, William Tracewell, and John G Jiang.
• Clinical Pharmacology, Cephalon, Inc., Frazer, Pennsylvania 19355, USA. mdarwish@celphalon.com
• Clin Drug Investig. 2007 Jan 1;27(9):605-11.

Background And ObjectivesPatients with cancer, particularly those undergoing chemotherapy or radiotherapy, may develop oral mucositis. This is the first study to investigate the absorption profile of fentanyl buccal tablet (FBT) - an effervescent formulation of fentanyl indicated for the management of breakthrough pain in opioid-tolerant cancer patients - in patients with or without oral mucositis.MethodsIn this open-label study, patients with or without oral mucositis self-administered a single 200 microg dose of FBT by placing the tablet between the upper gum and cheek above a molar tooth. Venous blood samples for measurement of plasma fentanyl concentrations were collected at regular intervals up to 8 hours following FBT administration. Parameters of interest included maximum plasma concentration (C(max)), time to reach C(max) (t(max)), area under the plasma concentration-time curve from time zero to 8 hours (AUC(8)), and AUC from time zero to the median t(max) (AUC(tmax)(')). Adverse events were monitored throughout the study. Oral mucosal examinations and measurements of vital signs were performed at intervals up to 8 hours following FBT administration.ResultsSixteen patients, 8 with and 8 without oral mucositis, received FBT and completed the study. The severity of oral mucositis was mild in the patients exhibiting this condition. Median C(max) values were comparable: 1.14 ng/mL (range 0.26-2.69 ng/mL) in patients with mucositis, and 1.21 ng/mL (range 0.21-2.34 ng/mL) in patients without mucositis. The t(max) was not significantly different in the two groups: median t(max) was 25.0 min (range 15-45 min) in patients with mucositis and 22.5 min (range 10-121 min) in patients without mucositis. Median AUC(tmax') values were 0.17 ng . h/mL (range 0.04-0.52 ng . h/mL) in patients with mucositis, and 0.20 ng . h/mL (range 0.00-0.65 ng . h/mL) in patients without mucositis. The corresponding AUC(8) values were 2.05 ng . h/mL (range 1.16-3.83 ng . h/mL) and 1.55 ng . h/mL (range 0.74-3.07 ng . h/mL), respectively. FBT was generally well tolerated in this small group. No application site adverse events or changes in oral mucosal assessments were reported.ConclusionThe absorption profile of a single dose of FBT 200 microg was similar in patients with or without mild oral mucositis. The compound was generally well tolerated.

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