Pan European Networks - Horizon 2020 - page 193

It has also been shown that bystanders administering IN
naloxone to overdose victims may save lives.
8
However, in one
study some bystanders were not able to connect the mucosal
atomising device to the syringe containing naloxone.
8
This
indicates that simpler devices such as a disposable, single-use
nasal sprayer may be beneficial in an acute situation when lay
people are involved.
Lack of knowledge
However, IN naloxone for bystander use is not established.
3,4,14
A
major issue is that there is practically no knowledge about the
pharmacokinetics of the nasal formulations used so far. Due to
low concentrations of naloxone used in previous nasal
administrations, it is likely that only a suboptimal amount of
naloxone ever reached the site of action in the brain.
Consequently, the potential of nasal administration in overdose
has not been properly evaluated, the efficacy of the treatment
may be severely underrated, and the place IN naloxone has in this
setting is not well established.
The present research group has significant experience with nasal
formulations and with pharmacokinetic studies of nasally
administered opioids and sedatives.
15-17
In this project a new formulation with a naloxone concentration
allows for administration of therapeutic doses comparable to
0.8mg IM in 100μl by a disposable unidose nasal sprayer.
Comparisons of the pharmacokinetics of different doses of the
nasal spray and IV and intramuscular naloxone in healthy
volunteers are on-going. Moreover, we also compare the
pharmacodynamics of nasal and intramuscular naloxone by
means of effects on pupil size and pain threshold in healthy
volunteers under opioid influence. A randomised clinical trial
comparing intramuscular and intranasal naloxone is in the
planning phase. And finally, an epidemiological study of long term
mortality of a cohort of non-fatal opioid overdoses in Oslo is also
on-going.
The preclinical studies in volunteers have thus far shown
promising results, which are satisfactory bioavailability and time to
maximum concentration of the nasal formulation. The formulation
is well-tolerated with no adverse events or discomfort.
Acknowledgements
The pre-formulation work was commissioned to Phatsawee
Jansook, PharmaD, PhD, Bangkok. Thanks to Professor Thorsteinn
Loftsson, University of Iceland, and Richard Poulsen, Azanta,
Denmark. PhD candidate Arne Kristian Skulberg, MD, Ida Tylleskär,
medical student, and consultants Fridtjof Heyerdahl, Anne
Cathrine Braarud and Professor P A Steen have all contributed
significantly to this project.
1
2
3
Kerr D, Kelly A M, Dietze P, Jolley D, Barger B. Randomized controlled trial
comparing the effectiveness and safety of intranasal and intramuscular
naloxone for the treatment of suspected heroin overdose.
Addiction.
2009;104:2067-74
4
Kelly A M, Kerr D, Dietze P, Patrick I,Walker T, and Koutsogiannis Z.
Randomised trial of intranasal versus intramuscular naloxone in prehospital
treatment for suspected opioid overdose.
Med J Aust.
2005;182:24-7
5
Sabzghabaee A M, Eizadi-Mood N,Yaraghi A, and Zandifar S. Naloxone
therapy in opioid overdose patients: intranasal or intravenous? A randomized
clinical trial.
Arch Med Sci.
2014;10:309-14
6
Community management of opioid overdose. Geneva: World Health
Organization; 2014
7
Kerr D, Dietze P, and Kelly A M. Intranasal naloxone for the treatment of
suspected heroin overdose.
Addiction.
2008;103:379-86
8
Doe-Simkins M,Walley A Y, Epstein A, and Moyer P. Saved by the nose:
bystander-administered intranasal naloxone hydrochloride for opioid
overdose.
Am J Public Health.
2009;99:788-91
9
Dowling J, Isbister G K, Kirkpatrick C M, Naidoo D, and Graudins A. Population
pharmacokinetics of intravenous, intramuscular, and intranasal naloxone in
human volunteers.
Ther Drug Monit.
2008;30:490-6
10
Loimer N, Hofmann P, and Chaudhry H R. Nasal Administration of Naloxone Is
as Effective as the Intravenous Route in Opiate Addicts.
Int J Addict.
1994;29:819-27
11
Kaufman R D, Gabathuler M L, and Bellville J W. Potency, duration of action
and pA2 in man of intravenous naloxone measured by reversal of morphine-
depressed respiration.
J Pharmacol Exp Ther.
1981;219:156-62
12
Ngai S H, Berkowitz BA,Yang J C, Hempstead J, and Spector S.
Pharmacokinetics of naloxone in rats and in man: basis for its potency and
short duration of action.
Anesthesiology.
1976;44:398-401
13
Ashton H, and Hassan Z. Best evidence topic report. Intranasal naloxone in
suspected opioid overdose.
Emerg Med J.
2006;23:221-3
14
Walley A Y, Xuan Z, Hackman H H, Quinn E, Doe-Simkins M, Sorensen-Alawad
A,
et al.
Opioid overdose rates and implementation of overdose education
and nasal naloxone distribution in Massachusetts: interrupted time series
analysis.
BMJ.
2013;346:f174
15
Dale O, Hoffer C, Sheffels P, and Kharasch E D. Disposition of nasal,
intravenous, and oral methadone in healthy volunteers.
Clin Pharmacol Ther.
2002;72:536-45
16
Dale O, Nilsen T, Loftsson T, Hjorth Tonnesen H, Klepstad P, Kaasa S,
et al.
Intranasal midazolam: a comparison of two delivery devices in human
volunteers.
J Pharm Pharmacol.
2006;58:1311-8
17
Moksnes K, Fredheim O M, Klepstad P, Kaasa S,Angelsen A, Nilsen T,
et al.
Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous
difference?
Eur J Clin Pharmacol.
2008;64:497-502
Professor Ola Dale, MD, PhD
Pain Group, Department of Circulation and Medical Imaging
Faculty of Medicine, Norwegian University of Science
andTechnology
Department of Research and Innovation
St Olav University Hospital
te l :
+47 72826401
H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L
I S S U E S I X
193
P R O F I L E
A D D I C T I O N
1...,183,184,185,186,187,188,189,190,191,192 194,195,196,197,198,199,200,201,202,203,...244
Powered by FlippingBook