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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 caffeine

Area 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 concentration

Metabolic 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

Page last updated: August 23, 2015

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