A change in plasma midazolam after an oral dose can begin before the drug reaches the liver. A mouse experiment with the herbal formula Banha-sasim-tang separated that possibility from the assumption that every oral midazolam change reflects CYP3A activity.
The investigators measured midazolam and its hydroxylated metabolite and examined the stomach environment and drug absorption. Their experiments supported reduced gastric absorption under the more acidic conditions associated with the formula. The finding matters because a smaller or later plasma signal after oral administration can result from a change in entry into circulation.
A route comparison, parent and metabolite time courses, and evidence about gastric pH can help distinguish altered absorption from altered clearance. In this paper, the formula, experimental timing and animal model define the evidence. The data cannot quantify the effect in a human patient taking a commercial preparation, whose formulation and other exposures may differ.