|
|
|
Day -1 |
Day 7 |
Day 14 |
Day 28 |
Day 42 |
Midazolam (po) |
Cmax (ng mL-1) |
n |
20 |
20 |
20 |
20 |
20 |
|
|
Mean ± SD |
30.9 ± 9.8 |
50.5 ± 14.1 |
56.6 ± 14.4 |
33.7 ± 11.5 |
33.3 ± 9.5 |
|
|
Geometric mean |
29.6 |
48.6 |
54.9 |
31.9 |
32.1 |
|
|
95% CI |
25.8 – 33.9 |
42.6 – 55.6 |
48.7 – 61.8 |
27.1 – 37.5 |
28.2 – 36.5 |
|
AUC0-t (ng h mL-1) |
n |
20 |
20 |
20 |
20 |
20 |
|
|
Mean ± SD |
74.5 ± 21.9 |
198.7 ± 52.2 |
225.1 ± 50.0 |
83.9 ± 26.1 |
80.1 ± 23.8 |
|
|
Geometric mean |
71.6 |
192.9 |
219.9 |
80.0 |
77.0 |
|
|
95% CI |
62.5 – 82.0 |
171.9 – 216.4 |
198.3 – 243.9 |
68.8 –
93.1 |
67.2 – 88.1 |
|
Tmax (h) |
n |
20 |
20 |
20 |
20 |
20 |
|
|
Median (min, max) |
0.5 (0.5, 1.0) |
0.5 (0.5, 2.0) |
0.5 (0.5, 2.0) |
0.5 (0.5, 1.0) |
0.5 (0.5, 2.0) |
|
t1/2 (h) |
n |
20 |
20 |
20 |
20 |
20 |
|
|
Mean ± SD |
4.4 ± 0.9 |
4.2 ± 0.8 |
4.3 ± 0.9 |
4.1 ± 0.9 |
4.3 ±
1.0 |
|
|
Geometric mean |
4.2 |
4.1 |
4.2 |
4.1 |
4.2 |
|
|
95% CI |
3.8 – 4.8 |
3.7 – 4.5 |
3.8 – 4.7 |
3.7 – 4.5 |
3.8 –
4.6 |
Prednisolone (po) |
Cmax (ng mL-1) |
n |
20 |
20 |
20 |
20 |
19 |
|
|
Mean ± SD |
156.1 ± 28.7 |
134.6 ± 21.3 |
138.0 ± 19.7 |
150.0 ±
28.6 |
134.4 ± 21.2 |
|
|
Geometric mean |
153.6 |
133.1 |
136.8 |
147.6 |
132.8 |
|
|
95% CI |
141.0 – 167.4 |
124.0 – 142.9 |
128.2 – 145.9 |
135.5
– 160.7 |
123.0 – 143.4 |
|
AUC0-t (ng h mL-1) |
n |
20 |
20 |
20 |
20 |
19 |
|
|
Mean ± SD |
571.6 ± 98.1 |
591.9 ± 76.4 |
631.0 ± 77.9 |
571.9 ±
96.5 |
553.2 ± 92.8 |
|
|
Geometric mean |
562.7 |
586.7 |
625.9 |
563.8 |
545.6 |
|
|
95% CI |
515.5 – 614.2 |
549.7 – 626.3 |
587.9- 666.4 |
519.2-
612.2 |
502.2- 592.8 |
|
Tmax (h) |
n |
20 |
20 |
20 |
20 |
19 |
|
|
Median (min, max) |
1.0 (0.5, 2.0) |
1.5 (0.5, 3.0) |
2.0 (0.5, 3.0) |
1.0 (0.5, 3.0) |
1.0 (0.5, 3.0) |
|
t1/2 (h) |
n |
20 |
20 |
20 |
20 |
19 |
|
|
Mean ± SD |
2.2 ± 0.3 |
2.2 ± 0.2 |
2.3 ± 0.2 |
2.3 ± 0.2 |
2.1 ±
0.3 |
|
|
Geometric mean |
2.2 |
2.2 |
2.3 |
2.2 |
2.1 |
|
|
95% CI |
2.1 – 2.3 |
2.1 – 2.3 |
2.2 – 2.4 |
2.1 – 2.4 |
2.0 –
2.2 |
Atorvastatin (po) |
Cmax (ng mL-1) |
n |
20 |
19 |
19 |
19 |
19 |
|
|
Mean ± SD |
3.2 ± 1.5 |
3.1 ± 1.4 |
4.0 ± 2.4 |
3.3 ± 1.4 |
3.2 ±
1.5 |
|
|
Geometric mean |
2.9 |
2.8 |
3.5 |
3.0 |
2.9 |
|
|
95% CI |
2.3 – 3.7 |
2.3 – 3.5 |
2.8 – 4.5 |
2.5 – 3.8 |
2.3 –
3.6 |
|
AUC0-t (ng h mL-1) |
n |
20 |
19 |
19 |
19 |
19 |
|
|
Mean ± SD |
16.1 ± 6.2 |
28.2 ± 12.1 |
33.8 ± 13.8 |
17.9 ± 6.8 |
18.2 ± 6.2 |
|
|
Geometric mean |
15.2 |
26.4 |
31.7 |
17.0 |
17.4 |
|
|
95% CI |
13.1 – 17.7 |
22.3 – 31.3 |
26.8 – 37.6 |
14.5 – 19.9 |
15.0 – 20.0 |
|
Tmax (h) |
n |
20 |
19 |
19 |
19 |
19 |
|
|
Median (min, max) |
0.5 (0.5, 3.0) |
3.0 (1.0, 10.0) |
2.0 (1.0,
10.0) |
0.5 (0.5, 6.0) |
0.5 (0.5, 2.0) |
|
t1/2 (h) |
n |
20 |
19 |
19 |
19 |
19 |
|
|
Mean ± SD |
9.2 ± 1.6 |
5.8 ± 1.3 |
4.5 ± 0.8 |
8.5 ± 2.2 |
8.5 ±
2.5 |
|
|
Geometric mean |
9.1 |
5.7 |
4.4 |
8.3 |
8.2 |
|
|
95% CI |
8.3 – 9.8 |
5.1 – 6.3 |
4.1 – 4.8 |
7.4 – 9.3 |
7.1 –
9.5 |
Midazolam (iv) |
AUC0-t (ng h mL-1) |
n |
20 |
19 |
19 |
19 |
19 |
|
|
Mean ± SD |
48.8 ± 12.1 |
67.4 ± 13.6 |
73.7 ± 14.5 |
56.0 ± 12.3 |
53.5 ± 11.6 |
|
|
Geometric Mean |
47.5 |
66.0 |
72.4 |
54.7 |
52.2 |
|
|
95% CI |
42.6 – 52.9 |
59.7 – 73.1 |
66.0 – 79.3 |
49.2 – 60.8 |
46.6 – 58.5 |
|
t1/2 (h) |
n |
20 |
19 |
19 |
19 |
19 |
|
|
Mean ± SD |
4.6 ± 1.5 |
4.5 ± 1.2 |
4.6 ± 1.0 |
4.0 ± 1.3 |
4.4 ±
1.5 |
|
|
Geometric Mean |
4.3 |
4.3 |
4.5 |
3.8 |
4.1 |
|
|
95% CI |
3.6 – 5.2 |
3.7 – 5.0 |
4.1 – 5.0 |
3.1 – 4.5 |
3.4 –
5.0 |