Enzyme measurements from a laboratory model and clearance measured in a living subject support different parts of a pharmacokinetic argument.
Nicoli and colleagues found changes in P450-related gene expression and reduced activity in several enzyme assays in mice lacking functional Npc1. They also used midazolam as a probe in living mice and observed altered clearance. The paper reported additional evidence of P450-system changes from a feline model and a limited set of human samples.
The midazolam clearance experiment was performed in mice. The human observations did not provide an individual midazolam clearance estimate. In assessing an opinion about a patient, identify which evidence concerns gene expression, enzyme activity or measured drug disposition, and which species supplied each result.
Nicoli et al., study of cytochrome P450 function in Niemann–Pick type C models (full text) · DOI