Pharmacokinetics and Pharmacodynamics of a New Formulation of Nasal Naloxone for Prehospital Use

Summary

Overdose with potential deadly outcome is a serious problem among opioid abusers, not least in Norway. The annual death toll from overdose is about 250, higher than road traffic accidents. Those who inject heroin or other opioids are considered to have the highest risk for death from overdose. To save lives, immediate treatment with a μ-opioid antidote such as naloxone is required. Usually naloxone is injected into a muscle or a blood vessel. Administration of naloxone via the nose (intranasal) has been suggested as an alternative for use by emergency teams and possibly also bystanders. This is not only an easier way to give naloxone, but would also eliminate the risk for needle stick injuries and blood contamination. In a series of studies on intranasal naloxone at The Norwegian University of Science and Technology, this study explores pharmacokinetics and pharmacodynamics of intranasal and intramuscular naloxone in healthy volunteers under the influence of remifentanil.

Conditions

• Drug Overdose

Interventions

DRUG

Intranasal naloxone

Administer 0,1 ml 8 mg/ml naloxone intranasally, dose = 0,8 mg naloxone

DRUG

Intramuscular naloxone

Administer 2 mL, dose intramuscular naloxone 0,8 mg

DRUG

Remifentanil

Administer remifentanil intravenously by way of Target Control Infusion, Minto model at a target of 2,5 ng/ml. This to achieve a state of safe and predictable opioid influence to assess pharmacodynamic response to naloxone. After treatment of 4 participants protocol amended 22. january 2015 to reduce remifentanil target to 1,25 ng/ml in the next 4. In the last 4 participants the dose will be decided later, but not exceed 2,5 ng/ml.

DEVICE

Aptar Unidose

This is the spray device chosen, and its function in this setting (spray up side down) will be assessed by weighing the device before and after administration.

Sponsors & Collaborators

• St. Olavs Hospital

  collaborator OTHER

• Norwegian University of Science and Technology

  lead OTHER

Principal Investigators

• Toril A Nagelhus Hernes, phd prof · Norwegian University of Science and Technology

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-12-31

Primary Completion

2015-04-30

Completion

2015-09-30

Countries

• Norway

Study Locations