Sample collection, analytical methods, and pharmacokinetic
analysis
Blood samples were collected for pharmacokinetics (PK) analysis of oral
midazolam, prednisolone, and atorvastatin at 0, 0.5, 1, 2, 3, 4, 6, 8,
10, 12, 24 h post dose on days -1, 7, 14, 28, and 42. For PK analysis of
intravenous midazolam, blood samples were collected at 0, 0.08, 0.17,
0.33, 0.5, 0.75, 1,1.5, 2, 4, 6, 8, 10, 12, and 24 h post dose on days
-1, 7, 14, 28, and 42. Plasma concentrations of all analytes were
measured by validated methods using liquid chromatography-tandem mass
spectrometry. The linear analytical range of the assay was 20 − 20000 pg
mL-1 for midazolam, 5 − 250 ng mL-1for prednisolone, and 50 − 10000 pg mL-1 for
atorvastatin.
The primary PK parameters analyzed for midazolam, prednisolone, and
atorvastatin included the AUC0-t, AUC from time of
dosing to infinity (AUC0‐inf), and Cmax.
Additional PK parameters included Tmax, and elimination
half‐life (t1/2).