Bioavailability of Dexmedetomidine After Intranasal Administration

Study Overview
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Brief Summary
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In a recent study by Yuen et al it was shown that preoperative intranasal administration of dexmedetomidine is a useful alternative for oral midazolam in children. However, there is no information on the pharmacokinetics of dexmedetomidine after intranasal administration. The aim of this study is to investigate the comparative pharmacokinetics of intranasally and intravenously administered dexmedetomidine in healthy volunteers. The absolute bioavailability of intranasally administered dexmedetomidine will be calculated. In addition, we will report the effects of intranasally and intravenously administered dexmedetomidine on plasma catecholamine levels, systemic blood pressure, heart rate and sedation. We will also monitor the local and systemic safety and tolerability of intranasally administered dexmedetomidine.

Official Title
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Bioavailability of Dexmedetomidine After Intranasal Administration in Healthy Subjects

Conditions
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Sedation

Intervention / Treatment
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* Drug: Intravenous dexmedetomidine
* Drug: Intranasal dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fluent skills in the Finnish language in order to be able to give informed consent and communicate with the study personnel. Age ≥ 18 years. Male gender. Weight ≥ 60 kg. Written informed consent from the subject. Exclusion Criteria: Previous history of intolerance to the study drug or related compounds and additives. Concomitant drug therapy of any kind except paracetamol in the 14 days prior to the study. Existing or recent significant disease. History of hematological, endocrine, metabolic or gastrointestinal disease. History of asthma or any kind of drug allergy. Previous or present alcoholism, drug abuse, psychological or other emotional problems that are likely to invalidate informed consent, or limit the ability of the subject to comply with the protocol requirements. Donation of blood within six weeks prior to and during the study. Special diet or lifestyle factors which would compromise the conditions of the study or the interpretation of the results. BMI > 30 kg / m2. Participation in any other clinical study involving investigational or marketed drug products concomitantly or within one month prior to the entry into this study. Smoking during one month before the start of the study or during the study period. Clinically significant abnormal findings in physical examination, ECG or laboratory screening [routine haematology (haemoglobin, haematocrit, red blood cell count, white blood cell count, platelets), renal function tests (creatinine, urea) and liver function tests (bilirubin)].

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous dexmedetomidine<br>Dexmedetomidine is administered intravenously | Drug: Intravenous dexmedetomidine<br>* 100 ug<br>|
| Experimental: Intranasal administration<br>Dexmedetomidine is administered intranasally | Drug: Intranasal dexmedetomidine<br>* 100 ug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The absolute bioavailability of intranasally administered dexmedetomidine |  | At baseline and 5, 10, 15, 20, 30, 45 min and 1, 1.5, 2, 3, 4, 5, 6, 8 and 10 h. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effects of intranasally and intravenously administered dexmedetomidine on plasma catecholamine levels, systemic blood pressure, heart rate and sedation, local and systemic safety and tolerability of intranasal dexmedetomidine. |  | At baseline and 5, 10, 15, 20, 30, 45 min and 1, 1.5, 2, 3, 5 and 10 h. Only local nasal tolerability is assessed at 5 and 10 h. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dexmedetomidine, intranasal, pharmacokinetics, pharmacodynamics