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

Healthy Volunteers Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01731067
• Other study ID #: Coktail DBS
• Status: Completed
• Phase: Phase 1
• First received: November 14, 2012
• Last updated: September 15, 2014
• Start date: November 2012
• Est. completion date: January 2014

Study information

• Verified date: September 2014
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Cocktail probe drugs

Locations

Country	Name	City	State
Switzerland	University Hospitals	Geneva 14

Sponsors (1)

Lead Sponsor	Collaborator
Jules Desmeules

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer		4 singles days spaced out with one week wash-out periods	No
Secondary	correlation between plasma or urine and capillary concentrations for each probe cocktail drug		4 singles days spaced out with one week wash-out periods	No
Secondary	comparison. between genotype and phenotype for each enzyme		one day	No