Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers
Arne Kristian Skulberg1,2, Ida Tylleskar1, Turid Nilsen1
1Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Post-Box 8905, 7491, Trondheim, Norway.
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.
More Related Videos
Related Concept Videos
Bioavailability Study Design: Healthy Subjects Versus Patients
Pharmacokinetics: Overview
Dynamic Equilibrium
Pharmacokinetic Models: Overview
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
Nonlinear Pharmacokinetics: Overview
Nonlinearity can arise due to the saturation of plasma protein-binding or...
Nonlinear Pharmacokinetics: Causes of Nonlinearity
Nonlinear drug absorption can occur when the process is rate-limited by solubility, carrier-mediated transport systems, or saturation of the presystemic gut wall or hepatic metabolism. For instance, high doses of riboflavin...


