The Effect of Obesity in Dexmedetomidine Metabolic Clearance
10. oktober 2016 oppdatert av: Pontificia Universidad Catolica de Chile
The purpose of this study is to study the effect of obesity in dexmedetomidine pharmacokinetics and pharmacodynamic profile.
Studieoversikt
Detaljert beskrivelse
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.
Studietype
Intervensjonell
Registrering (Forventet)
40
Fase
- Fase 4
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Región metropolitana
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Santiago, Región metropolitana, Chile
- Hospital Clinico Pontificia Universidad Catolica
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 60 år (Voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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.
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Dexmedetomidine 0.5 μg/kg over 10 minutes and then, 0.5 mcg/kg/h throughout surgery.
Andre navn:
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Eksperimentell: 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.
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Dexmedetomidine 0.5 μg/kg over 10 minutes and then, 0.5 mcg/kg/h throughout surgery.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Dexmedetomidine plasmatic levels
Tidsramme: 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
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Measured by high performance liquid chromatography
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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
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Steatohepatitis score
Tidsramme: 3 months after liver biopsy specimen collection
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Using liver biopsy, a score for steatohepatitis will be applied on samples from all patients
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3 months after liver biopsy specimen collection
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Plasma disappearance rate of indocyanine
Tidsramme: 2 hours after arrival to Post-Anesthesia Care Unit
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Using indocyanine green and LiMON monitor (Pulsion Medical Systems) surrogate measures of liver blood flow will be registered.
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2 hours after arrival to Post-Anesthesia Care Unit
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Enzyme expression
Tidsramme: 3 months after liver biopsy specimen collection
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Liver samples will be analyzed for UGT2B10 and UGT1A4 expression (involved in dexmedetomidine metabolization)
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3 months after liver biopsy specimen collection
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Hemodynamics
Tidsramme: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia
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Heart rate and arterial pressure will be recorded during anesthesia
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Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia
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Anesthetic depth
Tidsramme: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia
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Using a bispectral index monitor, anesthetic depth will be monitorized through out surgery.
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Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Etterforskere
- Hovedetterforsker: Luis I Cortínez, MD, Associate Professor Ordinary Category
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. august 2015
Primær fullføring (Forventet)
1. oktober 2016
Studiet fullført (Forventet)
1. desember 2017
Datoer for studieregistrering
Først innsendt
6. september 2015
Først innsendt som oppfylte QC-kriteriene
21. september 2015
Først lagt ut (Anslag)
23. september 2015
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
12. oktober 2016
Siste oppdatering sendt inn som oppfylte QC-kriteriene
10. oktober 2016
Sist bekreftet
1. oktober 2016
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Overernæring
- Ernæringsforstyrrelser
- Overvektig
- Kroppsvekt
- Overvekt
- Fysiologiske effekter av legemidler
- Adrenerge midler
- Nevrotransmittere agenter
- Molekylære mekanismer for farmakologisk virkning
- Sentralnervesystemdepressiva
- Agenter fra det perifere nervesystemet
- Analgetika
- Sensoriske systemagenter
- Analgetika, ikke-narkotisk
- Adrenerge alfa-2-reseptoragonister
- Adrenerge alfa-agonister
- Adrenerge agonister
- Hypnotika og beroligende midler
- Dexmedetomidin
Andre studie-ID-numre
- 14-253
- 1150197 (Annet stipend/finansieringsnummer: FONDECYT)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
UBESLUTTE
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