Evaluation of the Potential Pharmacokinetic Interactions Between Probe Drugs in the Geneva Phenotyping Cocktail

Jules Desmeules30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Drug Interaction

Outcomes

Primary Outcomes

Area under the capillary blood concentration-time curve (AUC) of caffeine

Comparison of caffeine AUC when treatment A or D is administered

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D

Area under the capillary blood concentration-time curve (AUC) of dextromethorphan

Comparison of dextromethorphan AUC when treatment A or D is administered

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D

Area under the capillary blood concentration-time curve (AUC) of flurbiprofen

Comparison of flurbiprofen AUC when treatment A or D is administered

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D

Area under the capillary blood concentration-time curve (AUC) of midazolam

Comparison of midazolam AUC when treatment A or D is administered

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D

Area under the capillary blood concentration-time curve (AUC) of omeprazole

Comparison of omeprazole AUC when treatment A or D is administered

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D

Area under the capillary blood concentration-time curve (AUC) of fexofenadine

Comparison of fexofenadine AUC when treatment B or D is administered

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment B or D

Area under the capillary blood concentration-time curve (AUC) of bupropion

Comparison of bupropion AUC when treatment C or D is administered

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post treatment C or D