PMID- 34880961
OWN - NLM
STAT- MEDLINE
DCOM- 20220114
LR  - 20220429
IS  - 1918-1523 (Electronic)
IS  - 1203-6765 (Print)
IS  - 1203-6765 (Linking)
VI  - 2021
DP  - 2021
TI  - Pharmacokinetic Characterisation and Comparison of Bioavailability of Intranasal 
      Fentanyl, Transmucosal, and Intravenous Administration through a Three-Way 
      Crossover Study in 24 Healthy Volunteers.
PG  - 2887773
LID - 10.1155/2021/2887773 [doi]
LID - 2887773
AB  - BACKGROUND: For more than 60 years, the synthetic opioid fentanyl has been widely 
      used in anaesthesia and analgesia. While the intravenous formulation is primarily 
      used for general anaesthesia and intensive care settings, the drug's high 
      lipophilic properties also allow various noninvasive routes of administration. 
      Published data suggest that intranasal administration is also attractive for use 
      as intranasal patient-controlled analgesia (PCA). A newly developed intranasal 
      fentanyl formulation containing 47 mug fentanyl, intravenous fentanyl, and oral 
      transmucosal fentanyl citrate were characterised, and bioavailability was 
      compared to assess the suitability of the intranasal formulation for an 
      intranasal PCA product. METHODS: 27 healthy volunteers were enrolled in a 
      single-centre, open-label, randomised (order of treatments), single-dose study in 
      a three-period crossover design. The pharmacokinetics of one intranasal puff of 
      fentanyl formulation (47 mug, 140 mL per puff), one short intravenous infusion of 
      50 mug fentanyl, and one lozenge with an integrated applicator (200 mug fentanyl) 
      were studied, and bioavailability was calculated. Blood samples were collected 
      over 12 hours, and plasma concentrations of fentanyl were determined by HPLC with 
      MS/MS detection. RESULTS: 24 volunteers completed the study. The geometric mean 
      of AUC(0-tlast) was the highest with oral transmucosal administration 
      (1106 h  * pg/ml, CV% = 32.86), followed by intravenous (672 h  * pg/ml, 
      CV% = 32.18) and intranasal administration (515 h  * pg/ml, CV% = 30.10). C (max) 
      was 886 pg/ml (CV% = 59.38) for intravenous, 338 pg/ml (CV% = 45.61) for 
      intranasal, and 310 pg/ml (CV% = 29.58) for oral transmucosal administration. t 
      (max) was shortest for intravenous administration (0.06 h, SD = 0.056), followed 
      by intranasal (0.21 h, SD = 0.078) and oral transmucosal administration (1.20 h, 
      SD = 0.763). Dose-adjusted absolute bioavailability was determined to be 74.70% 
      for the intranasal formulation and 41.25% for the oral transmucosal product. In 
      total, 38 adverse events (AEs) occurred. Fourteen AEs were potentially related to 
      the investigational items. No serious AE occurred. CONCLUSION: Pharmacokinetic 
      parameters and bioavailability of the investigated intranasal fentanyl indicated 
      suitability for its intended use as an intranasal PCA option.
CI  - Copyright (c) 2021 S. Nardi-Hiebl et al.
FAU - Nardi-Hiebl, S
AU  - Nardi-Hiebl S
AUID- ORCID: 0000-0003-3563-3505
AD  - Department of Anaesthesia and Intensive Care, University Hospital Marburg, 
      Marburg, Germany.
FAU - Ndieyira, J W
AU  - Ndieyira JW
AUID- ORCID: 0000-0002-3466-7327
AD  - Division of Medicine, University College London, London, UK.
FAU - Al Enzi, Y
AU  - Al Enzi Y
AD  - Department of Mathematics and Natural Science, Gulf University of Science and 
      Technology, Mubarak Al-Abdullah, Kuwait.
FAU - Al Akkad, W
AU  - Al Akkad W
AUID- ORCID: 0000-0002-0109-3021
AD  - Royal Free London Hospital, University College London, London, UK.
FAU - Koch, T
AU  - Koch T
AD  - Department of Anaesthesia and Intensive Care, University Hospital Marburg, 
      Marburg, Germany.
FAU - Geldner, G
AU  - Geldner G
AD  - Department of Anaesthesiology Intensive Care Medicine Emergency Medicine and Pain 
      Therapy, RKH Kliniken-Hospital Ludwigsburg, Ludwigsburg, Germany.
FAU - Reyher, C
AU  - Reyher C
AD  - Department of Anaesthesiology Intensive Care Medicine Emergency Medicine and Pain 
      Therapy, Klinikum Kassel GmbH, Kassel, Germany.
FAU - Eberhart, L H J
AU  - Eberhart LHJ
AD  - Department of Anaesthesia and Intensive Care, University Hospital Marburg, 
      Marburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20211129
PL  - United States
TA  - Pain Res Manag
JT  - Pain research & management
JID - 9612504
RN  - UF599785JZ (Fentanyl)
SB  - IM
MH  - Administration, Intranasal
MH  - Administration, Intravenous
MH  - Administration, Mucosal
MH  - Administration, Oral
MH  - Area Under Curve
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - *Fentanyl
MH  - Healthy Volunteers
MH  - Humans
MH  - Infusions, Intravenous
MH  - *Tandem Mass Spectrometry
PMC - PMC8648480
COIS- SNH and LE are co-inventors of the aforementioned intranasal PCA device under 
      development. The other co-authors do not have anything to declare.
EDAT- 2021/12/10 06:00
MHDA- 2022/01/15 06:00
PMCR- 2021/11/29
CRDT- 2021/12/09 07:01
PHST- 2021/10/04 00:00 [received]
PHST- 2021/10/25 00:00 [revised]
PHST- 2021/11/16 00:00 [accepted]
PHST- 2021/12/09 07:01 [entrez]
PHST- 2021/12/10 06:00 [pubmed]
PHST- 2022/01/15 06:00 [medline]
PHST- 2021/11/29 00:00 [pmc-release]
AID - 10.1155/2021/2887773 [doi]
PST - epublish
SO  - Pain Res Manag. 2021 Nov 29;2021:2887773. doi: 10.1155/2021/2887773. eCollection 
      2021.