The Effect of Obesity in Dexmedetomidine Metabolic Clearance

Pontificia Universidad Catolica de Chile40 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

Conditions

Obesity

Interventions

DexmedetomidineDRUG

Dexmedetomidine 0.5 μg/kg over 10 minutes and then, 0.5 mcg/kg/h throughout surgery.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Hospital Clinico Pontificia Universidad Catolica

Santiago, Santiago Metropolitan, Chile

Outcomes

Primary Outcomes

Dexmedetomidine plasmatic levels

Measured by high performance liquid chromatography

Time frame: 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

Steatohepatitis score

Using liver biopsy, a score for steatohepatitis will be applied on samples from all patients

Time frame: 3 months after liver biopsy specimen collection

Plasma disappearance rate of indocyanine

Using indocyanine green and LiMON monitor (Pulsion Medical Systems) surrogate measures of liver blood flow will be registered.

Time frame: 2 hours after arrival to Post-Anesthesia Care Unit

Enzyme expression

Liver samples will be analyzed for UGT2B10 and UGT1A4 expression (involved in dexmedetomidine metabolization)

Time frame: 3 months after liver biopsy specimen collection

Hemodynamics

Heart rate and arterial pressure will be recorded during anesthesia

Time frame: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia

Anesthetic depth

Using a bispectral index monitor, anesthetic depth will be monitorized through out surgery.

Time frame: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia

Data from ClinicalTrials.gov

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