Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot
Information source: University Hospital, Geneva
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy Volunteers
Intervention: Cocktail probe drugs (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Jules Desmeules Official(s) and/or principal investigator(s): Jules A Desmeules, Pr, Principal Investigator, Affiliation: University Hospital, Geneva
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.
Clinical Details
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer
Secondary outcome: correlation between plasma or urine and capillary concentrations for each probe cocktail drugcomparison. between genotype and phenotype for each enzyme
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Male.
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
Locations and Contacts
University Hospitals, Geneva 14, Switzerland
Additional Information
Starting date: November 2012
Last updated: September 15, 2014
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