Pharmacokinetics and Pharmacodynamics of Oral Transmucosal Dexmedetomidine. (OTM/DEX/PK)

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

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.

Study Overview

• Status: Completed
• Conditions: Sedation
• Intervention / Treatment: Drug: OTM Dexmedetomidine 1µg/ kg.; Drug: OTM Dexmedetomidine 0.75µg/ kg.; Drug: OTM Dexmedetomidine 0.5µg/ kg.

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Assiut Governorate
    • Asyut, Assiut Governorate, Egypt, 715715
      • South Egypt Cancer Institute, Assiut University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: DEX I; 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.; Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure.; Other Names: Precedex
ACTIVE_COMPARATOR: DEX II; 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.; Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure.; Other Names: Precedx
ACTIVE_COMPARATOR: DEX III; 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.; Oral transmucosal dexmedetomidine pharmacologically prepared as a jel substance will be administered to the buccal mucosa 30 mins before the operative procedure.; Other Names: Precedex

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Saher A Mohamed, MD, Assistant professor in anesthesia and pain management, South Egypt Cancer Institute, faculty of medicine, Assiut university.

Publications and helpful links

General Publications

• Mohamed SA, Abdel-Ghaffar HS, Hassan NA, El Sherif FA, Shouman SA, Omran MM, Hassan SB, Allam AAAE, Sayed DG. Pharmacokinetics and Pharmacodynamics of 3 Doses of Oral-Mucosal Dexmedetomidine Gel for Sedative Premedication in Women Undergoing Modified Radical Mastectomy for Breast Cancer. Anesth Analg. 2021 Feb 1;132(2):456-464. doi: 10.1213/ANE.0000000000005108.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 5, 2017
• Primary Completion (ACTUAL): June 1, 2019
• Study Completion (ACTUAL): July 1, 2019

Study Registration Dates

• First Submitted: April 5, 2017
• First Submitted That Met QC Criteria: April 15, 2017
• First Posted (ACTUAL): April 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 1, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: IORG0006563/no. 377

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes