The Effect of Obesity in Dexmedetomidine Metabolic Clearance

Pontificia Universidad Catolica de Chile

Status and phase: Unknown; Phase 4

Conditions: Obesity

Treatments: Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other

Identifiers

NCT02557867

1150197 (Other Grant/Funding Number)

14-253

Details and patient eligibility

About

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

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

40 participants in 2 patient groups

Obese

Experimental group

Description:

Body composition measurement before surgery using Dual energy X-ray absorptiometry. Dexmedetomidine infusion during surgery. Venous blood sampling for dexmedetomidine plasmatic levels during and after surgery. Liver blood flow indirect non-invasive assessment after surgery using indocyanine. Liver biopsy during surgery.

Treatment:

Drug: Dexmedetomidine

Non-obese

Experimental group

Description:

Body composition measurement before surgery using Dual energy X-ray absorptiometry. Dexmedetomidine infusion during surgery. Venous blood sampling for dexmedetomidine plasmatic levels during and after surgery. Liver blood flow indirect non-invasive assessment after surgery using indocyanine. Liver biopsy during surgery.

Treatment:

Drug: Dexmedetomidine