Pharmacokinetics and Pharmacodynamics of Oral Transmucosal Dexmedetomidine.

Study Overview
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Brief Summary
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Oral trans-mucosal administration is relatively easy and convenient, it also reduces first pass metabolism and has been used successfully for fentanyl, ketamine, and midazolam premedication.

Detailed Description
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The alpha2-adrenoceptor agonist, dexmedetomidine, was originally developed as a sedative and analgesic drug for use in intensive care. However, it has a number of unique pharmacodynamic properties, which also make it useful in anesthesia including; decreased MAC, analgesia without respiratory depression and a significant reduction in catecholamine secretion. Also it has been used off-label as an adjunctive agent for sedation and analgesia in patients in the critical care unit and for sedation during non-invasive procedures in radiology. It also has a potential role as part of anesthesia care to prevent emergence delirium and post-anesthesia shivering. Oral trans-mucosal administration is relatively easy and convenient, it also reduces first pass metabolism and has been used successfully for fentanyl, ketamine, and midazolam premedication. The current literature is focused in studying the sedative and analgesic effects of intravenously administered dexmedetomidine. Pharmacodynamics and pharmacokinetic studies undertaken on alternative routes of dexmedetomidine administration are lacking. The pharmacokinetic properties of trans-mucosal administration of dexmedetomidine have been demonstrated in one study only, and the clinical effects of non-parenteral administration of dexmedetomidine have been described in anecdotal case reports.

Official Title
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Pharmacokinetics and Pharmacodynamics of Three Doses of Oral Trans-mucosal Dexmedetomidine for Premedication in Patients Undergoing Modified Radical Mastectomy

Conditions
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Sedation

Intervention / Treatment
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* Drug: OTM Dexmedetomidine 1µg/ kg.
* Drug: OTM Dexmedetomidine 0.75µg/ kg.
* Drug: OTM Dexmedetomidine 0.5µg/ kg.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA physical status I - II. Aged between 20 and 60 years. Scheduled for modified radical mastectomy Exclusion Criteria: Cardiac disease. Hepatic disease. Renal disease. History of alcohol or drug abuse. Patients with a known allergy to the study drug

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pharmacokinetic and pharmacodynamic study of three different doses of oral transmucosal dexmedetomidine
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DEX I<br>OTM Dexmetetomidine 1µg/kg Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure. | Drug: OTM Dexmedetomidine 1µg/ kg.<br>* Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure.<br>* Other names: Precedex;|
| Active Comparator: DEX II<br>OTM Dexmetetomidine0.75µg/kg Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure. | Drug: OTM Dexmedetomidine 0.75µg/ kg.<br>* Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure.<br>* Other names: Precedx;|
| Active Comparator: DEX III<br>OTM Dexmetetomidine 0.5µg/kg. Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure. | Drug: OTM Dexmedetomidine 0.5µg/ kg.<br>* Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure.<br>* Other names: Precedex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Two milliliters of blood will be collected for determination of Peak Plasma Concentration (Cmax) | 360 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sedation preoperative | Sedation score is recorded pre-operatively every 5minutes for 30 minutes after OTM DEX administration | 30 minutes | 
| Blood pressure preoperative | Non invasive blood pressure will be recorded every 5 minutes for 30 minutes after OTM DEX administration. | 30 minutes. | 
| Heart rate preoperative | Heart rate will be recorded every 5 minutes for 30 minutes after OTM DEX administration. | 30 minutes | 
| Area under the plasma concentration versus time curve (AUC) | Two milliliters of blood will be collected for determination of Area under the plasma concentration versus time | 360 minutes. |