Clinical trial NCT02557867: The Effect of Obesity in Dexmedetomidine Metabolic Clearance
Official title: The Effect of Obesity in Dexmedetomidine Metabolic Clearance
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Obesity
Keywords: dexmedetomidine
pharmacokinetic
obesity
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
First posted: 2015-09-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: The purpose of this study is to study the effect of obesity in dexmedetomidine pharmacokinetics and pharmacodynamic profile.

Detailed description: The investigators expect to find an inverse correlation between the amount of fat mass and liver blood flow or with the enzymatic metabolic capacity. Results will be based on a population pharmacokinetic modeling analysis performed in NONMEM program. The investigators will first account for the effect of different measured size scalars on volumes and clearances and then they will search for plausible covariates (liver blood flow, enzymatic capacity, degree of hepatic steatosis, etc) on dexmedetomidine metabolic clearance. A pharmacokinetic model capable of characterizing clearance changes in the obese using more plausible biological covariates will be tried to be defined.

Eligibility criteria: Inclusion Criteria for obese patients:

* American Society of Anesthesiology classification I-III patients.
* Both genders.
* Age between 18 - 60 years.
* Body mass index higher than 40 Kg/m2.

Inclusion Criteria for non-obese patients:

* American Society of Anesthesiology classification I-II patients
* Both genders.
* Age between 18 - 60 years
* Body mass index lower than 30 Kg/m2.

Exclusion Criteria:

* Known allergy to study drugs
* Uncontrolled hypertension.
* Heart block greater than first degree.
* Chronic hepatic and kidney disease.
* Patients taking any drug acting in the central nervous system within 24 hrs before surgery.
* Patients taking drugs that induce overexpression of liver cytochrome P450-complex enzymes (Carbamazepine, Phenytoin, Phenobarbital, Rifampicin, Dexamethasone, Griseofulvin, Terbinafine, Prednisone, Hydrocortisone, Modafinil).)
* Known addiction to illicit drugs.
* Pregnancy.
* Current or past oncologic disease.

Primary outcomes:
measure: Dexmedetomidine plasmatic levels
timeFrame: From start of infusion (min): 5, 10, 20, 30, 45, 60, 90, 120, 150, 180; from end of infusion (min): 5, 10, 20, 30, 60, 90, 120, 240, 360, 720
Secondary outcomes:
measure: Steatohepatitis score
timeFrame: 3 months after liver biopsy specimen collection
measure: Plasma disappearance rate of indocyanine
timeFrame: 2 hours after arrival to Post-Anesthesia Care Unit
measure: Enzyme expression
timeFrame: 3 months after liver biopsy specimen collection
measure: Hemodynamics
timeFrame: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia
measure: Anesthetic depth
timeFrame: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Hospital Clinico Pontificia Universidad Catolica
state: Región metropolitana
Study officials:
affiliation: Associate Professor Ordinary Category
name: Luis I Cortínez, MD
role: PRINCIPAL_INVESTIGATOR
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