An in-vitro interaction signal needs exposure context before it predicts a clinical interaction.
Laboratory testing suggested tenapanor could inhibit CYP3A4/5. In a healthy-volunteer study, oral midazolam was administered alone and again after repeated tenapanor dosing. The midazolam area-under-the-curve ratio was 107%, with a 90% confidence interval of 101–113%; peak concentration and metabolite results were also similar.
The study tested a specific regimen in healthy volunteers. It does not establish the absence of every interaction at other doses, in severe illness or with additional medicines. Similar pharmacokinetics also do not directly measure every psychomotor or subjective effect.
For expert interpretation, distinguish enzyme inhibition at an experimental concentration from drug exposure achieved in the body. Identify route, dose and co-medication before extrapolation. This is a useful example of clinical probe-substrate evidence qualifying a laboratory concern without erasing the limits of the tested conditions.
Source: Publication PMC5599994, read from the supplied PDF. Applications to expert analysis are interpretation.
Related reading: Metamizole Reduced Midazolam Exposure in a Human CYP-Probe Experiment.