Table S1.
Midazolam study: pharmacokinetic parameters of midazolam and midazolam + riociguat in smokers and nonsmokers
| Nonsmokers | Smokers | |||||||
|---|---|---|---|---|---|---|---|---|
| Midazolam 7.5 mg (n = 12) | Midazolam 7.5 mg + riociguat 2.5 mg (n = 12) | Midazolam 7.5 mg (n = 8) | Midazolam 7.5 mg + riociguat 2.5 mg (n = 10) | |||||
| Parameter | Geometric mean (range) |
CV, % | Geometric mean (range) |
CV, % | Geometric mean (range) |
CV, % | Geometric mean (range) |
CV, % |
| AUC, μg·h/L | 83.5 (48.8–169.3) | 39.7 | 93.8 (48.9–174.0) | 43.7 | 103.8 (80.2–146.1) | 20.1 | 103.7 (67.5–147.1) | 28.9 |
| Cmax, μg/L | 24.5 (17.2–42.2) | 24.0 | 27.5 (14.5–48.1) | 36.4 | 35.4 (18.4–70.6) | 56.9 | 32.0 (18.5–74.9) | 47.6 |
| tmax, hours | 1.0 (0.5–4.0) | … | 1.0 (0.5–4.0) | … | 0.5 (0.5–2.0) | … | 1.0 (0.5–2.0) | … |
| t1/2, hours | 5.0 (3.3–7.9) | 29.1 | 4.1 (2.6–7.6) | 32.4 | 3.9 (2.2–8.3) | 41.7 | 4.6 (2.9–9.3) | 38.7 |
Note
Data are means, except tmax, which is a median. AUC0-∞: area under the plasma concentration–time curve; Cmax: maximum plasma concentration; CV: coefficient of variation; tmax: time to reach Cmax; t1/2: elimination half-life.