A drug can be affected by an enzyme and also change how that enzyme handles other medicines. Townsend and colleagues used several phase 1 comparisons to investigate both directions for isavuconazole.
With rifampin, isavuconazole exposure over a dosing interval was 90% lower under the tested regimen. In a separate comparison, ketoconazole increased isavuconazole exposure extrapolated from dosing to infinity by 422%. These experiments changed a co-medication and measured the antifungal.
In another part of the program, the investigators measured oral midazolam with and without isavuconazole. Midazolam exposure extrapolated to infinity increased by 103% and its peak increased by 72%. Those percentages describe midazolam under the tested regimen. They cannot be reversed to estimate what midazolam does to isavuconazole or applied to every other CYP3A substrate.
In a toxicology review, record the measured analyte, route, timing and interaction direction before using a study ratio. The trials measured pharmacokinetics in healthy participants and did not establish the severity of sedation in a particular patient.