The Effect of Obesity in Dexmedetomidine Metabolic Clearance

NCT02557867 | Unknown Phase 4 DMC

• 2 other identifiers: 14-2531150197
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Obesity

Keywords

dexmedetomidine; pharmacokinetic; obesity

Outcome Measures

Primary Outcomes (1)

• Dexmedetomidine plasmatic levels

  Measured by high performance liquid chromatography

  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 (5)

• Steatohepatitis score

  3 months after liver biopsy specimen collection

• Plasma disappearance rate of indocyanine

  2 hours after arrival to Post-Anesthesia Care Unit

• Enzyme expression

  3 months after liver biopsy specimen collection

• Hemodynamics

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

• Anesthetic depth

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

Study Arms (2)

Obese

EXPERIMENTAL

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.

Drug: Dexmedetomidine

Non-obese

EXPERIMENTAL

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.

Drug: Dexmedetomidine

Interventions

Dexmedetomidine DRUG

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

Also known as: Precedex

Non-obese; Obese

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• American Society of Anesthesiology classification I-III patients.
• Both genders.
• Age between 18 - 60 years.
• Body mass index higher than 40 Kg/m2.
• American Society of Anesthesiology classification I-II patients
• Both genders.
• Age between 18 - 60 years
• Body mass index lower than 30 Kg/m2.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Hospital Clinico Pontificia Universidad Catolica

Santiago, Santiago Metropolitan, Chile

Location

Related Publications (13)

• Han PY, Duffull SB, Kirkpatrick CM, Green B. Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther. 2007 Nov;82(5):505-8. doi: 10.1038/sj.clpt.6100381.

  PMID: 17952107 BACKGROUND

• Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004 Aug;58(2):119-33. doi: 10.1111/j.1365-2125.2004.02157.x.

  PMID: 15255794 BACKGROUND

• Casati A, Putzu M. Anesthesia in the obese patient: pharmacokinetic considerations. J Clin Anesth. 2005 Mar;17(2):134-45. doi: 10.1016/j.jclinane.2004.01.009.

  PMID: 15809132 BACKGROUND

• Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg. 2000 Mar;90(3):699-705. doi: 10.1097/00000539-200003000-00035.

  PMID: 10702460 BACKGROUND

• Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum-Ping ST, Moretti EW, Young CC, Wright DR, Macleod DB, Somma J. Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology. 2004 Nov;101(5):1066-76. doi: 10.1097/00000542-200411000-00005.

  PMID: 15505441 BACKGROUND

• Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN, Ozcan B. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anaesth. 2006 Jul;53(7):646-52. doi: 10.1007/BF03021622.

  PMID: 16803911 BACKGROUND

• Kaivosaari S, Toivonen P, Aitio O, Sipila J, Koskinen M, Salonen JS, Finel M. Regio- and stereospecific N-glucuronidation of medetomidine: the differences between UDP glucuronosyltransferase (UGT) 1A4 and UGT2B10 account for the complex kinetics of human liver microsomes. Drug Metab Dispos. 2008 Aug;36(8):1529-37. doi: 10.1124/dmd.108.021709. Epub 2008 May 12.

  PMID: 18474681 BACKGROUND

• Bedogni G, Agosti F, De Col A, Marazzi N, Tagliaferri A, Sartorio A. Comparison of dual-energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance analysis for the assessment of body composition in morbidly obese women. Eur J Clin Nutr. 2013 Nov;67(11):1129-32. doi: 10.1038/ejcn.2013.159. Epub 2013 Sep 11.

  PMID: 24022260 BACKGROUND

• Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999 Sep;94(9):2467-74. doi: 10.1111/j.1572-0241.1999.01377.x.

  PMID: 10484010 BACKGROUND

• Li W, Zhang Z, Wu L, Tian Y, Feng S, Chen Y. Determination of dexmedetomidine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a pharmacokinetic study. J Pharm Biomed Anal. 2009 Dec 5;50(5):897-904. doi: 10.1016/j.jpba.2009.06.012. Epub 2009 Jun 16.

  PMID: 19577876 BACKGROUND

• Ji QC, Zhou JY, Gonzales RJ, Gage EM, El-Shourbagy TA. Simultaneous quantitation of dexmedetomidine and glucuronide metabolites (G-Dex-1 and G-Dex-2) in human plasma utilizing liquid chromatography with tandem mass spectrometric detection. Rapid Commun Mass Spectrom. 2004;18(15):1753-60. doi: 10.1002/rcm.1548.

  PMID: 15282775 BACKGROUND

• Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CM. A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet. 2004;43(15):1167-78. doi: 10.2165/00003088-200443150-00007.

  PMID: 15568893 BACKGROUND

• Rolle A, Paredes S, Cortinez LI, Anderson BJ, Quezada N, Solari S, Allende F, Torres J, Cabrera D, Contreras V, Carmona J, Ramirez C, Oliveros AM, Ibacache M. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients. Br J Anaesth. 2018 May;120(5):969-977. doi: 10.1016/j.bja.2018.01.040. Epub 2018 Mar 28.

  PMID: 29661414 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Luis I Cortínez, MD

  Associate Professor Ordinary Category

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2015
• First Posted: September 23, 2015
• Study Start: August 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: December 1, 2017
• Last Updated: October 12, 2016

Record last verified: 2016-10

Locations

CL (1)