Effect of buccal dwell time on the pharmacokinetic profile of fentanyl buccal tablet.
BACKGROUND
The time fentanyl buccal tablet (FBT) takes to completely dissolve after placement on the buccal mucosa (i.e., 'dwell time') could exceed the time to onset of analgesia.


OBJECTIVE
To examine the relationship between FBT dwell time and fentanyl pharmacokinetic parameters.


METHODS
This was a post hoc exploratory analysis of data from two randomized, open-label, crossover, pharmaco-kinetic studies that were designed to assess dose proportionality within the anticipated therapeutic dose range. Healthy adults received single FBT doses of 200-1080 microg in Study 1 (n = 28) and 270-1300 microg in Study 2 (n = 42).


METHODS
Assessments included buccal dwell time, defined as the duration of FBT presence in the oral cavity, and the following pharmacokinetic measures: maximum serum concentration (C(max)), time to C(max) (T(max)) and area under the concentration-time curve (AUC; exposure) from 0 minutes to median T(max) adjusted for the dose (T(max')) (AUC(0 T(max'))). Spontaneously reported adverse events were recorded.


RESULTS
Mean buccal dwell time for FBT across the dose range varied from 14 to 25 minutes (range 3 - 62 minutes). There was no evidence of an association between FBT dwell time and values for T(max) (medians 45 - 60 minutes), dose-normalized C(max) (means 0.42-0.66 pg/ml/200 microg) or dose-normalized AUC(0 T(max')) (means 0.24-0.38 pg x h/ml/200 microg) over the range of FBT doses delivered. All adverse events reported were mild to moderate; none were unexpected or serious.


CONCLUSIONS
The pharmacokinetic parameters of FBT did not appear to be related to its buccal dwell time.
Darwish
M
M
Clinical Pharmacology, Cephalon, Inc., Frazer, PA 19355, USA. mdarwish@cephalon.com
Kirby
M
M
Jiang
J G
JG
D000278:Administration, Buccal; D000328:Adult; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated; D005283:Fentanyl