Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.
Eur J Clin Pharmacol
; 74(7): 873-883, 2018 Jul.
Article
em En
| MEDLINE
| ID: mdl-29568976
ABSTRACT
PURPOSE:
This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg.METHODS:
Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured.RESULTS:
The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference.CONCLUSIONS:
A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. TRIAL REGISTRATION clinicaltrials.gov NCT02307721.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Analgésicos Opioides
/
Modelos Biológicos
/
Naloxona
/
Antagonistas de Entorpecentes
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Noruega