Clinical trial NCT01731067: Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2012-11-21
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer
timeFrame: 4 singles days spaced out with one week wash-out periods
Secondary outcomes:
measure: correlation between plasma or urine and capillary concentrations for each probe cocktail drug
timeFrame: 4 singles days spaced out with one week wash-out periods
measure: comparison. between genotype and phenotype for each enzyme
timeFrame: one day
Other outcomes:
Locations:
city: Geneva 14
country: Switzerland
facility: University Hospitals
Study officials:
affiliation: University Hospital, Geneva
name: Jules A Desmeules, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bosilkovska M, Samer CF, Deglon 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.