Evaluation of the Potential Pharmacokinetic Interactions Between Probe Drugs in the Geneva Phenotyping Cocktail
Status:
Completed
Trial end date:
2015-04-01
Target enrollment:
Participant gender:
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.