Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot
Status:
Completed
Trial end date:
2014-01-01
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.
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.