When a drug is swallowed, intestinal metabolism can change how much reaches the bloodstream. An IV dose bypasses that first step, which can help distinguish an intestinal interaction from an effect on systemic clearance.
The review describes a crossover study in 16 healthy volunteers. With simeprevir, the oral midazolam area under the curve to the last measured time was 1.45 times the comparator value. The parent-to-metabolite ratio increased with oral midazolam, while the corresponding increase was absent with IV midazolam. The authors interpreted that pattern as consistent with mild intestinal CYP3A inhibition.
The oral probe was given separately and the IV probe as part of a cocktail. When citing this study, specify the route and measured endpoint. The oral ratio cannot be applied directly to an IV dose or converted into an estimate of sedation.
Review of clinical simeprevir interaction studies (full text) ยท DOI