Nishioka and colleagues compared ordinary midazolam solution with two liposomal preparations, one with a polyethylene glycol (PEG) coating and one without. They characterized the particles, administered the preparations to rabbits and measured plasma midazolam. A formulation change can alter exposure even when the active drug has the same name.
The uncoated liposomal preparation produced a larger area under the plasma concentration–time curve than ordinary solution after oral administration. The investigators did not find that advantage for the PEG-coated formulation versus ordinary solution. The coated preparation also had a greater proportion of larger particles, so the comparison reflects the formulations as prepared, including differences in particle characteristics.
The concentration–time curve measures systemic exposure. The authors proposed reduced first-pass loss as an explanation for the uncoated preparation’s result, but the comparison does not independently quantify the gut and liver contributions. For a toxicology interpretation, record the route, formulation and blood-draw times before comparing concentrations. The rabbit experiment provides a formulation-specific observation and leaves human exposure and clinical effects to separate studies.
Nishioka et al., BMC Pharmacology and Toxicology (2025) · Full text