Results:
The Cmax and AUC0-t of oral midazolam
before administration of carotegrast methyl was 30.9 ± 9.8 ng
mL-1 and 74.5 ± 21.9 ng h mL-1,
respectively. The geometric mean ratio of the Cmax and
AUC0-t of midazolam on day 14 to those on day -1 was
1.86 (90% CI, 1.64 – 2.11) and 3.07 (90% CI, 2.81 – 3.35), which did
not fall within the range of 0.80 – 1.25, suggesting that carotegrast
methyl had a PK interaction with midazolam. Similar PK interactions were
found for intravenous midazolam and atorvastatin, but not for
prednisolone. The inhibitory effect of carotegrast methyl on
CYP3A4-mediated metabolism of midazolam and atorvastatin had almost
disappeared by 14 days after the end of administration.