EVIDENCE LIBRARY
A Geneva phenotyping cocktail altered fexofenadine exposure without identifying one responsible probe
A healthy-volunteer study found an interaction in a multi-drug cocktail that included low-dose midazolam.
A healthy-volunteer study found an interaction in a multi-drug cocktail that included low-dose midazolam.
The crossover finding
Thirty volunteers participated in a randomized four-way crossover study of enzyme and transporter probes. Fexofenadine exposure fell when given in the full Geneva cocktail, which included caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam. Its area under the curve decreased by 43% and peak concentration by 49%.
The study did not identify which individual probe, or combination of probes, caused the fexofenadine change. It reported no interaction among the remaining probes under the tested conditions.
Do not attribute the cocktail effect to midazolam alone
The presence of midazolam in a combination does not establish it as the responsible interacting agent. Nor does a low-dose phenotyping study establish the effects of therapeutic sedation regimens. The investigators called for further mechanistic work.
For interpretation, specify the full mixture, the affected drug, and the measured pharmacokinetic endpoint. This paper demonstrates an unexpected limitation of simultaneous probing, not a proven pairwise midazolam-fexofenadine interaction.
Source paper
Original analysis of the supplied journal article, identified as PMC6963818.