PMID- 25901479
OWN - NLM
STAT- MEDLINE
DCOM- 20150707
LR  - 20181202
IS  - 1551-7489 (Print)
IS  - 1551-7489 (Linking)
VI  - 11
IP  - 2
DP  - 2015 Mar-Apr
TI  - Effect of dosing interval on pharmacokinetics of fentanyl pectin nasal spray from 
      a crossover study.
PG  - 139-46
LID - jom.2015.0263 [pii]
LID - 10.5055/jom.2015.0263 [doi]
AB  - OBJECTIVE: To evaluate the effects of different dosing intervals on multiple-dose 
      pharmacokinetics, and safety and tolerability of fentanyl pectin nasal spray 
      (FPNS). METHODS: This was an open-label study in healthy volunteers. Five FPNS 
      treatments (1 x 100 mug; 2 x 100 mug at 4-, 2-, and 1-hour intervals, and 8 x 100 
      mug consecutively) were administered to the right nostril, with a >/= 3-day washout 
      period. Blood samples were collected at predose and up to 1,440 minutes postdose. 
      Plasma fentanyl concentrations were determined. Pharmacokinetic parameters-peak 
      concentration (C(max)), time to C(max) (t(max)), and area under the 
      concentration-time curve (AUC)-were derived using noncompartmental method. For 
      the two-dose regimens, pharmacokinetic parameters were compared between doses 
      using a paired t-test with p < 0.05 as statistically significant. RESULTS: 
      Thirteen subjects were enrolled and 10 completed the study. Median tmax was 10-15 
      minutes across five regimens. Cmax post the second dose significantly increased 
      for 1-hour (p < 0.0001) and 2-hour (p < 0.001) but not 4-hour intervals (p = 
      0.462). C(max) and AUC(0-24) following 8 x 100 mug were approximately fivefold of 
      those following 1 x 100 mug. Dizziness (11.9 percent) and somnolence (4.9 percent) 
      were most common adverse events (AEs). 12.9 percent of patients discontinued due 
      to AEs. CONCLUSIONS: FPNS exhibited consistently rapid t(max). When intervals 
      between two doses were shorter, the difference in C(max) between the first and 
      second dose was larger. All regimens of FPNS were well tolerated. Exposure 
      reached a plateau after eight consecutive doses, suggesting potential limited 
      absorption through the nasal mucosa.
FAU - Chen, Cuiping
AU  - Chen C
AD  - Research & Development, Depomed Inc., Newark, California.
FAU - Bujanover, Shay
AU  - Bujanover S
AD  - Research & Development, Depomed Inc., Newark, California.
FAU - Gupta, Anita
AU  - Gupta A
AD  - Vice Chair, Associate Professor, Division of Pain Medicine and Regional 
      Anesthesiology, Department of Anesthesiology and Perioperative Medicine, Drexel 
      University College of Medicine, Philadelphia, Pennsylvania.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Opioid Manag
JT  - Journal of opioid management
JID - 101234523
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Drug Combinations)
RN  - 0 (Nasal Sprays)
RN  - 89NA02M4RX (Pectins)
RN  - UF599785JZ (Fentanyl)
SB  - IM
MH  - Administration, Intranasal
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Analgesics, Opioid/administration & dosage/pharmacokinetics
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Female
MH  - Fentanyl/administration & dosage/*pharmacokinetics
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nasal Sprays
MH  - Pain/*drug therapy/metabolism
MH  - Pectins/administration & dosage/*pharmacokinetics
MH  - Retrospective Studies
MH  - Young Adult
EDAT- 2015/04/23 06:00
MHDA- 2015/07/08 06:00
CRDT- 2015/04/23 06:00
PHST- 2015/04/23 06:00 [entrez]
PHST- 2015/04/23 06:00 [pubmed]
PHST- 2015/07/08 06:00 [medline]
AID - jom.2015.0263 [pii]
AID - 10.5055/jom.2015.0263 [doi]
PST - ppublish
SO  - J Opioid Manag. 2015 Mar-Apr;11(2):139-46. doi: 10.5055/jom.2015.0263.