The Effect of Obesity in Dexmedetomidine Metabolic Clearance

NCT ID: NCT02557867

Last Updated: 2016-10-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2017-12-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Obesity

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

NONE

Study Groups

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Obese

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.

Group Type EXPERIMENTAL

Dexmedetomidine

Intervention Type DRUG

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

Non-obese

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.

Group Type EXPERIMENTAL

Dexmedetomidine

Intervention Type DRUG

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

Interventions

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Dexmedetomidine

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

Intervention Type DRUG

Other Intervention Names

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Precedex

Eligibility Criteria

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Inclusion Criteria

* 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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Luis I Cortínez, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor Ordinary Category

Locations

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Hospital Clinico Pontificia Universidad Catolica

Santiago, Santiago Metropolitan, Chile

Site Status

Countries

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Chile

References

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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.

Reference Type BACKGROUND
PMID: 17952107 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15255794 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15809132 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10702460 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15505441 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16803911 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18474681 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24022260 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10484010 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19577876 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15282775 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15568893 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29661414 (View on PubMed)

Other Identifiers

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1150197

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

14-253

Identifier Type: -

Identifier Source: org_study_id

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