title: Absorption of fentanyl from fentanyl buccal tablet in cancer patients with or without oral mucositis: a pilot study.
abstract: OBJECTIVE
  Patients 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Sixteen 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.
  
  
  CONCLUSIONS
  The 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.
authors: Clinical Pharmacology, Cephalon, Inc., Frazer, Pennsylvania 19355, USA. mdarwish@celphalon.com
authors: Mona
authors: M
authors: Darwish
authors: Mary
authors: M
authors: Kirby
authors: Philmore
authors: P
authors: Robertson
authors: William
authors: W
authors: Tracewell
authors: John G
authors: JG
authors: Jiang
mesh_terms: D000042:Absorption; D000278:Administration, Buccal; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000009:adverse effects; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010414:Pennsylvania; D010865:Pilot Projects; D011878:Radiotherapy / Q000009:adverse effects; D012720:Severity of Illness Index; D013280:Stomatitis / Q000150:complications / Q000209:etiology / Q000378:metabolism*; D013607:Tablets
chemical_list: D000701:Analgesics, Opioid; D000970:Antineoplastic Agents; D013607:Tablets; D005283:Fentanyl
references: Clin Pharmacokinet. 2005;44(12):1279-86
references: 16372825
references: Cancer Nurs. 2004 May-Jun;27(3):183-205
references: 15238805
references: Cancer Control. 1999 Mar;6(2):136-145
references: 10758542
references: Support Care Cancer. 2001 Jun;9(4):247-57
references: 11430420
references: Oral Oncol. 1998 Jan;34(1):39-43
references: 9659518
references: Pain. 1999 May;81(1-2):129-34
references: 10353500
references: Oncol Nurs Forum. 1998 Oct;25(9):1623-6
references: 9802057
references: Br J Haematol. 2000 Aug;110(2):292-9
references: 10971384
references: Clin Ther. 2006 May;28(5):707-14
references: 16861092
references: J Pain Symptom Manage. 1995 Apr;10(3):243-8
references: 7629418
references: Oncol Nurs Forum. 2002 Aug;29(7):1051-7
references: 12183754
references: Clin J Pain. 2006 Nov-Dec;22(9):805-11
references: 17057563