TABLE 4

Summary of plasma midazolam and 1′-hydroxymidazolam pharmacokinetic parameters by the noncompartmental method

Data are median for Tmax, geometric mean (90% confidence intervals) for geometric mean ratio to day 1 for Cmax and AUCinf, and mean ± S.D. for other parameters.

nCmaxTmaxAUCinft1/2CL/FGeometric Mean Ratio to Day 1 for CmaxaGeometric Mean Ratio to Day 1 for AUCinfaMetabolic Ratiob
ng/mlhng · h/mlhl/h
Midazolam
    Day 1229.99 ± 3.700.5022.2 ± 9.003.74 ± 1.95108 ± 58.5
    Day 152215.9 ± 5.480.5044.6 ± 23.74.13 ± 1.9354.1 ± 21.61.62 (1.46, 1.80)1.97 (1.78, 2.18)
    Day 22229.80 ± 4.570.5023.0 ± 11.33.75 ± 2.10106 ± 48.00.97 (0.88, 1.08)1.02 (0.92, 1.13)
    Day 292210.5 ± 4.960.5022.9 ± 11.63.76 ± 3.39105 ± 41.71.04 (0.94, 1.15)1.01 (0.91, 1.12)
1′-Hydroxymidazolam
    Day 1224.57 ± 1.860.509.08 ± 3.353.32 ± 3.380.422 ± 0.161
    Day 15224.70 ± 2.280.7511.1 ± 3.593.46 ± 3.370.272 ± 0.104
    Day 22223.77 ± 1.530.508.49 ± 3.763.02 ± 2.550.388 ± 0.152
    Day 29225.18 ± 2.660.509.50 ± 4.122.28 ± 1.250.441 ± 0.179
  • a Primary parameters for drug-drug interaction assessment.

  • b Supportive evidence for drug-drug interaction: AUCinf ratio 1′-hydroxymidazolam/midazolam, multiplied by 326 (molecular weight of midazolam) and divided by 342 (molecular weight of 1′-hydroxymidazolam).