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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jules Desmeules, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01731067
First received: November 14, 2012
Last updated: September 15, 2014
Last verified: September 2014

November 14, 2012
September 15, 2014
November 2012
May 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01731067 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot
Not Provided

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Healthy Volunteers
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: 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
    Intervention: Drug: Cocktail probe drugs
  • Active Comparator: CYP2D6 and P-gp inhibitor
    Oral intake of quinidine (200 mg) before oral intake of the cocktail probe drugs
    Intervention: Drug: Cocktail probe drugs
  • 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
    Intervention: Drug: Cocktail probe drugs
  • 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)
    Intervention: Drug: Cocktail probe drugs
Bosilkovska M, Samer CF, Déglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
January 2014
May 2013   (final data collection date for primary outcome measure)

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
Male
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT01731067
Coktail DBS
No
Jules Desmeules, University Hospital, Geneva
Jules Desmeules
Not Provided
Principal Investigator: Jules A Desmeules, Pr University Hospital, Geneva
University Hospital, Geneva
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP