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Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot

This study is currently recruiting participants.
Verified November 2012 by University Hospital, Geneva
Sponsor:
Information provided by (Responsible Party):
Jules Desmeules, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01731067
First received: November 14, 2012
Last updated: November 20, 2012
Last verified: November 2012
History of Changes
  Purpose

Phenotyping is an approach largely used for the evaluation of the activity of cytochromes and transporters in vivo. It consists of the administration of probe substances metabolised by a specific cytochrome or transported by P-glycoprotein (P-gp) for example, followed by the determination of a metabolic ratio or the evaluation of the plasmatic or urinary concentrations of the probe substances. The administration of a cocktail containing several probe substances allows the simultaneous evaluation of the activity of several cytochromes and P-gp in a single test.

The aim of this project is the validation of a phenotyping cocktail of low dose probe drugs for the assessment of cytochrome P450 and P-gp activities by simple capillary blood sampling and dried blood spot (DBS) analysis. The cocktail consists of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam and fexofenadine for the simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CAP2C19, CYP2D6, CYP3A4 and P-gp, respectively.

The modulation of the activity of cytochromes or P-gp will be evaluated by the administration of inhibitors (fluvoxamine, voriconazole, quinidine) or inducer (rifampicin) of the metabolic pathways or the P-gp mediated transport.


Condition Intervention Phase
Healthy Volunteers
 Drug: Cocktail probe drugs
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic

Resource links provided by NLM:

MedlinePlus related topics: Caffeine Rashes
U.S. FDA Resources

Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer [ Time Frame: 4 singles days spaced out with one week wash-out periods ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • correlation between plasma or urine and capillary concentrations for each probe cocktail drug [ Time Frame: 4 singles days spaced out with one week wash-out periods ] [ Designated as safety issue: No ]
  • comparison. between genotype and phenotype for each enzyme [ Time Frame: one day ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: November 2012
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors
Oral intake of fluvoxamine (50 mg per day during 2 days) and voriconazole (400 mg) before oral intake of the cocktail probe drugs
 Drug: Cocktail probe drugs
Other Names:
  • Oral intake of the cocktail probe drugs :
  • bupropion 25 mg
  • flurbiprofen 25 mg
  • omeprazole 5 mg
  • dextromethorphan 5 mg
  • midazolam 1 mg
  • fexofenadine 25mg
  • Caffeine (a cup of coffee)
Active Comparator: CYP2D6 and P-gp inhibitor
Oral intake of quinidine (200 mg) before oral intake of the cocktail probe drugs
 Drug: Cocktail probe drugs
Other Names:
  • Oral intake of the cocktail probe drugs :
  • bupropion 25 mg
  • flurbiprofen 25 mg
  • omeprazole 5 mg
  • dextromethorphan 5 mg
  • midazolam 1 mg
  • fexofenadine 25mg
  • Caffeine (a cup of coffee)
Active Comparator: CYPs and P-gp inducer
Oral intake of rifampicin (600 mg per day during 7 days) before oral intake of the cocktail probe drugs
 Drug: Cocktail probe drugs
Other Names:
  • Oral intake of the cocktail probe drugs :
  • bupropion 25 mg
  • flurbiprofen 25 mg
  • omeprazole 5 mg
  • dextromethorphan 5 mg
  • midazolam 1 mg
  • fexofenadine 25mg
  • Caffeine (a cup of coffee)
Experimental: Probe cocktail alone

Oral intake of the cocktail probe drugs :

  • bupropion 25 mg
  • flurbiprofen 25 mg
  • omeprazole 5 mg
  • dextromethorphan 5 mg
  • midazolam 1 mg
  • fexofenadine 25mg
  • Caffeine (a cup of coffee)
 Drug: Cocktail probe drugs
Other Names:
  • Oral intake of the cocktail probe drugs :
  • bupropion 25 mg
  • flurbiprofen 25 mg
  • omeprazole 5 mg
  • dextromethorphan 5 mg
  • midazolam 1 mg
  • fexofenadine 25mg
  • Caffeine (a cup of coffee)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male volunteers aged from 18 to 60 years
  • BMI between 18 and 25
  • Understanding of French language and able to give a written inform consent.

Exclusion Criteria:

  • Smoker
  • Taking drugs which alter CYPs activity
  • Renal or hepatic impairment
  • Medical history of porphyria
  • Medical history of chronic alcoholism or abuse of psychoactive drugs
  • Liver transplantation
  • Sensitivity to any of the drugs used
  • Wearing contact lenses (risk of coloration with rifampicin)
  • ECG showing long QT interval (>0.46sec)
  • Alteration of hepatic tests
  • Presenting genetic polymorphism of poor CYP 2B6, 2C9, 2C19, 2D6 metabolisers
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01731067

Contacts
Contact: Jules A Desmeules, Pr jules.desmeules@hcuge.ch
Contact: Marija Bosilkovska, Pharm D marija.bosilkovska@hcuge.ch

Locations
Switzerland
University Hospitals Recruiting
Geneva 14, Switzerland
Principal Investigator: Jules A Desmeules, Pr            
Sponsors and Collaborators
Jules Desmeules
Investigators
Principal Investigator: Jules A Desmeules, Pr University Hospital, Geneva
  More Information

No publications provided

Responsible Party: Jules Desmeules, Pr, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01731067     History of Changes
Other Study ID Numbers: Coktail DBS
Study First Received: November 14, 2012
Last Updated: November 20, 2012
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Caffeine
Dextromethorphan
Midazolam
Flurbiprofen
Bupropion
Omeprazole
Fexofenadine
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antitussive Agents
Respiratory System Agents
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous

ClinicalTrials.gov processed this record on May 16, 2013