The Effect of Obesity in Dexmedetomidine Metabolic Clearance
- Registration Number
- NCT02557867
- Lead Sponsor
- Pontificia Universidad Catolica de Chile
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 40
Not provided
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Obese Dexmedetomidine 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. Non-obese Dexmedetomidine 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.
- Primary Outcome Measures
Name Time Method Dexmedetomidine plasmatic levels 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 Measured by high performance liquid chromatography
- Secondary Outcome Measures
Name Time Method Steatohepatitis score 3 months after liver biopsy specimen collection Using liver biopsy, a score for steatohepatitis will be applied on samples from all patients
Plasma disappearance rate of indocyanine 2 hours after arrival to Post-Anesthesia Care Unit Using indocyanine green and LiMON monitor (Pulsion Medical Systems) surrogate measures of liver blood flow will be registered.
Enzyme expression 3 months after liver biopsy specimen collection Liver samples will be analyzed for UGT2B10 and UGT1A4 expression (involved in dexmedetomidine metabolization)
Hemodynamics Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia Heart rate and arterial pressure will be recorded during anesthesia
Anesthetic depth Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia Using a bispectral index monitor, anesthetic depth will be monitorized through out surgery.
Trial Locations
- Locations (1)
Hospital Clinico Pontificia Universidad Catolica
🇨🇱Santiago, Región metropolitana, Chile