Using tissue from the same donor does not make two experimental preparations interchangeable.
A study compared donor-matched human hepatocytes and liver microsomes using several probe drugs, including midazolam. Differences in enzyme enrichment and intracellular exposure helped explain some, but not all, disagreement in intrinsic clearance estimates.
The systems capture different biological processes. Scaling by protein amounts or unbound exposure did not fully reconcile absolute values, and neither preparation alone reproduces an intact patient.
Identify the test system behind a metabolic claim. A microsomal result should not be presented as a measured human clearance or directly converted into a dosing history. The study explains why assay preparation and scaling assumptions matter when interpreting benzodiazepine interaction predictions.
Source: PMC8041379, supplied full-text paper. Findings are paraphrased; forensic implications are an interpretation.
Related: Phenobarbital Versus Lorazepam: All-Cause Readmission Was Different From Alcohol-Related Readmission.