A phase 1 interaction study used midazolam as a probe of CYP3A activity. Thirty healthy volunteers took a 4 mg oral dose of midazolam alone and, after a washout and repeated eluxadoline doses, took the same midazolam dose alongside eluxadoline. The comparison used each participant as their own reference, in a fixed treatment order.
Midazolam’s geometric mean peak concentration ratio was 99.0% with a 90% confidence interval of 91.6% to 107.0%. The ratio for area under the concentration curve to the last measured point was 90.5%, with a 90% interval of 83.9% to 97.6%. The peak and area answer different questions. The peak describes the highest measured concentration, while the area integrates concentrations across sampling times. Both intervals fell within the study’s equivalence bounds for pharmacokinetic interpretation.
The results support a limited conclusion about midazolam exposure under the tested regimen in healthy volunteers. The trial measured plasma concentrations and used a single midazolam dose in each period. If the case question concerns clinical sedation, repeated midazolam dosing, or a patient with a different medical history, identify the additional evidence needed for that question before relying on the interaction study.