PMID- 19915714
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211020
IS  - 1753-5174 (Print)
IS  - 1753-5174 (Electronic)
IS  - 1753-5174 (Linking)
VI  - 1
IP  - 2
DP  - 2008 Sep
TI  - Extent of Fentanyl Accumulation Following Multiple Doses of Fentanyl Buccal 
      Tablet 400 microg in Healthy Japanese Volunteers.
PG  - 50-55
AB  - OBJECTIVE: This study was conducted to characterize the pharmacokinetics, 
      including extent of accumulation, and safety and tolerability of fentanyl 
      following multiple doses of fentanyl buccal tablet (FBT) in healthy Japanese 
      volunteers. METHODS: Healthy Japanese adults received 10 successive doses of 
      open-label FBT 400 microg at 6-hour intervals. Naltrexone was given to minimize 
      the opioid effects of fentanyl. FBT was placed above a molar tooth between the 
      gum and cheek. Peak serum fentanyl concentration (C(max)), time to C(max) 
      (t(max)), and area under the serum fentanyl concentration-time curve from 0 to 6 
      hours (AUC(0-6)) were summarized using descriptive statistics. Accumulation ratio 
      was calculated as C(max) for dose 10/C(max) for dose 1, and was calculated 
      similarly for AUC(0-6). RESULTS: Fourteen volunteers (mean age 33 years) were 
      enrolled, and 13 completed the study. After doses 1 and 10, respectively, mean 
      (SD) C(max) was 1.70 (0.49) ng/mL and 1.97 (0.42) ng/mL, AUC(0-6) was 4.46 (1.14) 
      ng.h/mL and 6.81 (0.90) ng.h/mL, and median (range) t(max) was 50 (30-110) 
      minutes and 30 (15-120) minutes. Following 10 successive doses, systemic exposure 
      (AUC(0-6)) was 55% higher than after dose 1, and C(max) was 23% higher. Steady 
      state was achieved within 3 days of dosing at 6-hour intervals, i.e., prior to 
      dose 10. The most frequent adverse events (AEs) were somnolence (N = 9), 
      decreased oxygen saturation (N = 4), headache (N = 3), application-site pain (N = 
      8), application-site erythema (N = 6), and application-site reaction (N = 5). All 
      AEs were mild or moderate. CONCLUSIONS: Following administration of FBT at 6-hour 
      intervals to healthy Japanese volunteers, at steady state, fentanyl exposure was 
      higher by 55% (AUC(0-6)) and 23% (C(max)) than after a single dose of FBT. 
      Adverse events were mild or moderate.
FAU - Darwish, Mona
AU  - Darwish M
FAU - Tempero, Kenneth
AU  - Tempero K
FAU - Jiang, John G
AU  - Jiang JG
FAU - Simonson, Philip G
AU  - Simonson PG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arch Drug Inf
JT  - Archives of drug information
JID - 101322852
PMC - PMC2773539
EDAT- 2008/09/01 00:00
MHDA- 2008/09/01 00:01
CRDT- 2009/11/17 06:00
PHST- 2009/11/17 06:00 [entrez]
PHST- 2008/09/01 00:00 [pubmed]
PHST- 2008/09/01 00:01 [medline]
AID - 10.1111/j.1753-5174.2008.00008.x [doi]
PST - ppublish
SO  - Arch Drug Inf. 2008 Sep;1(2):50-55. doi: 10.1111/j.1753-5174.2008.00008.x.