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Pharmacokinetic Study of Dexmedetomidine After Intra-Nasal and Buccal Dosing in Children

Phase 1
Completed
Conditions
Heart Diseases
Interventions
Registration Number
NCT03668951
Lead Sponsor
Children's Hospital Medical Center, Cincinnati
Brief Summary

This research study is a continuation of a previous DEX PK study. It is examining the absorption of Dexmedetomidine (DEX) in the blood when given orally and as a nasal spray. This study will help us determine the best dosing amount for children undergoing sedation or anesthesia with DEX.

Detailed Description

The study will be a prospective study of plasma concentrations after intranasal or buccal DEX to determine the early pharmacokinetics and bioavailability of a single dose via nasal or oral administration.

Dexmedetomidine sedation is commonly used at Cincinnati Children's Medical Center and other pediatric institutions. This compound is typically delivered intravenously or intranasally for sedation in children with or without congenital heart disease. Intranasal DEX is very effective for sedation although it has significant variability in the onset and peak effect. Patient care will be improved if factors that determine this variability can be determined. Investigators will determine the important clinical variables of peak plasma DEX concentration (Tmax and Cmax) of intranasal and buccal DEX in children.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
Inclusion Criteria
  • Children aged 6 - 48 months (inclusive) scheduled to receive anesthesia for elective cardiac surgery
  • The subject must be a candidate to receive Dex as determined by one of the study cardiac anesthesiologists
  • The attending cardiac anesthesiologists for the case and the Chief of Anesthesia Cardiac Anesthesia will concur with or veto this decision
  • The subjects legally authorized representative has given written informed consent to participate in the study
Exclusion Criteria
  • Post-natal age less than 6 months
  • The subject is allergic to or has had a contraindication to Dex
  • Severely depressed ventricular function on preoperative echocardiogram
  • The subject has a high risk of cardiac conduction system disease in the judgement of the attending anesthesiologist or cardiologist
  • The subject has a hemodynamically significant aortic coarctation or other left heart outflow obstruction
  • The subject has received digoxin, beta-adrenergic antagonist, or calcium channel antagonist on the day of surgery
  • The subject has received Dex within 1 week of the study date
  • Patients who are to receive intranasal Dex are excluded if they have nasal/respiratory symptoms, which in the opinion of the study anesthesiologist, may affect intranasal drug absorption

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Buccal DEX 2 mcg/kgDexmedetomidine buccalStandard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia, placement of an endotracheal tube and an arterial line. Once these are accomplished, Dexmedetomidine is administered according to group assignment.
Intranasal DEX 3 mcg/kgDexmedetomidine IntranasalStandard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia, placement of an endotracheal tube and an arterial line. Once these are accomplished, Dexmedetomidine is administered according to group assignment.
Intranasal DEX 4 mcg/kgDexmedetomidine IntranasalStandard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia, placement of an endotracheal tube and an arterial line. Once these are accomplished, Dexmedetomidine is administered according to group assignment.
Primary Outcome Measures
NameTimeMethod
Maximum blood concentration level of Dex - CmaxBlood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .

Dex concentration will be measured in the blood to determine the time point with the maximum concentration (Cmax).

The amount of time that Dex is present at the maximum concentration - TmaxBlood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .

Dex concentration will be measured in the blood to determine the time point with the maximum concentration and how long that maximum concentration lasts.

Secondary Outcome Measures
NameTimeMethod
Adverse events associated with Dex administrationParticipants will be followed until cardiopulmonary bypass, an expected duration of 2 hours.

Heart rate will be recorded by clinical staff prior to the procedure and continuously during the procedure. The heart rate during the time of study blood collection will be compared to the baseline vitals to determine is any adverse events occurred.

Area under the curve for Dex concentration levelsBlood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .

Dex concentration will be measured in the blood samples.

Bioavailability of intranasal Dex relative to intravenous Dex for distribution - plasma concentrationBlood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .

Data will also be analyzed using population modeling using nonlinear mixed effect modeling (NONMEM). Investigators will be measuring for approximately one half-life of Dex. This will allow us to estimate the important clinical parameter of relative bioavailability of intranasal vs intravenous Dex.

Bioavailability of IN Dex relative to intravenous Dex for elimination - plasma concentration.Blood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .

Data will also be analyzed using population modeling using nonlinear mixed effect modeling (NONMEM). Investigators will be measuring for approximately one half-life of Dex. This will allow us to estimate the important clinical parameter of relative bioavailability of intranasal vs intravenous Dex.

Systolic and diastolic blood pressure with Dex administrationParticipants will be followed until cardiopulmonary bypass, an expected duration of 2 hours.

Systolic and diastolic blood pressure will be recorded by clinical staff prior to the procedure and continuously during the procedure. The systolic and diastolic blood pressure during the time of study blood collection will be compared to the baseline blood pressure to determine is any adverse events occurred.

Trial Locations

Locations (1)

Joanna Paquin

🇺🇸

Cincinnati, Ohio, United States

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