Evaluation of the Potential Pharmacokinetic Interactions Between Probe Drugs in the Geneva Phenotyping Cocktail
Information source: University Hospital, Geneva
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Drug Interaction
Intervention: Caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam (Drug); Bupropion (Drug); Fexofenadine (Drug)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: Jules Desmeules
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.
When a cocktail approach is used it is important to make sure that no drug-drug interactions
occur between the probes within the cocktail. The validation of the lack of interactions,
which is the aim of the study, consists of demonstrating that there is no difference in the
pharmacokinetic parameters and/or metabolic ratios when a probe is administered alone or as
part of the cocktail. The Geneva 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.
Probe and metabolite concentrations will be measured in capillary blood using a dried blood
spot (DBS) analysis. To further facilitate sampling, a new simple device will be used to
ensure the precision of capillary blood collection.
Clinical Details
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: Area under the capillary blood concentration-time curve (AUC) of caffeineArea under the capillary blood concentration-time curve (AUC) of dextromethorphan Area under the capillary blood concentration-time curve (AUC) of flurbiprofen Area under the capillary blood concentration-time curve (AUC) of midazolam Area under the capillary blood concentration-time curve (AUC) of omeprazole Area under the capillary blood concentration-time curve (AUC) of fexofenadine Area under the capillary blood concentration-time curve (AUC) of bupropion
Secondary outcome: Metabolic ratio (MR) of paraxanthine blood concentration /caffeine blood concentrationMetabolic ratio (MR) of dextrorphan blood concentration /dextromethorphan blood concentration Metabolic ratio (MR) of 4-hydroxyflurbiprofen blood concentration /flurbiprofen blood concentration Metabolic ratio (MR) of 1-hydroxymidazolam blood concentration /midazolam blood concentration Metabolic ratio (MR) of 5-hydroxyomeprazole blood concentration /omeprazole blood concentration Metabolic ratio (MR) of 4-hydroxybupropion blood concentration /bupropion blood concentration Number of adverse events
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Healthy volunteers aged from 18 to 60 years
- BMI between 18 and 27
- Understanding of French language and able to give a written inform consent.
Exclusion Criteria:
- smoker
- pregnant women
- taking drugs which alter cytochrome P450 (CYP) activity
- renal or hepatic impairment
- medical history of chronic alcoholism or abuse of psychoactive drugs
- liver transplantation
- sensitivity to any of the drugs used
- Alteration of hepatic tests, more than 2x normal (aspartate transaminase >100U/L ;
alanine transaminase >100 units/L ; gamma-glutamyl transferase >80 units/L ;
bilirubin >50µmol/L)
- Presenting genetic polymorphism of poor CYP2C9, CYP2C19, CYP2D6 metabolizer
Locations and Contacts
Centre de Recherche Clinique, HUG, Rue Gabrielle Perret-Gentil 4, Genève 1211, Switzerland
Additional Information
Starting date: November 2014
Last updated: March 12, 2015
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