M Darwish1, M Kirby, J G Jiang. 1. Clinical Pharmacology, Cephalon, Inc., Frazer, PA 19355, USA. mdarwish@cephalon.com
Abstract
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. RESEARCH DESIGN AND 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). MAIN OUTCOME MEASURES: 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. CONCLUSION: The pharmacokinetic parameters of FBT did not appear to be related to its buccal dwell time.
RCT Entities:
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. RESEARCH DESIGN AND 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). MAIN OUTCOME MEASURES: 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. CONCLUSION: The pharmacokinetic parameters of FBT did not appear to be related to its buccal dwell time.