Table 1.
Pharmacokinetic parameter estimates of roflumilast and roflumilast N-oxide after administration of a single oral dose of roflumilast 500 µg alone and after co-administration with steady-state rifampicin
| Compound | Roflumilast | Roflumilast N-oxide | ||||
|---|---|---|---|---|---|---|
| Parameter | Roflumilast alone (n= 16) | Roflumilast and rifampicin (n= 15) | Ratio test : reference (90% CI) | Roflumilast alone (n= 16) | Roflumilast and rifampicin (n= 15) | Ratio test : reference (90% CI) |
| AUC0–∞ (h µg l−1)* | 38.5 (24.1–61.5) | 7.8 (5.4–11.4) | 0.21 (0.16, 0.27)‡ | 414.1 (275.6–622.2) | 180.2 (141.0–230.2) | 0.44 (0.36, 0.55)‡ |
| AUC0–last (h µg l−1)* | 35.1 (21.7–56.7) | 6.5 (4.5–9.4) | 0.19 (0.15, 0.25)‡ | 368 (279.5–484.3) | 177.0 (138.5–226.3) | 0.49 (0.41, 0.57)‡ |
| CL/F (l h−1)* | 13.0 (8.1–20.8) | 64.1 (44.0–93.4) | 4.84 (3.70, 6.32)‡ | NA | NA | NA |
| Cmax (µg l−1)* | 6.9 (4.9–9.7) | 2.2 (1.7–2.8) | 0.32 (0.26, 0.39)‡ | 9.5 (7.6–11.7) | 12.2 (10.1–14.8) | 1.30 (1.15, 1.48)‡ |
| tmax (h)† | 0.9 (0.6–1.5) | 1.0 (0.7–1.3) | NA | 6.5 (3.5–12.2) | 2.6 (1.7–4.0) | NA |
| t1/2 (h)* | 15.7 (9.4–26.3) | 6.0 (3.2–11.2) | 0.33 (0.23, 0.47) | 24.0 (15.3–37.5) | 9.9 (8.2–12.0) | 0.41 (0.33, 0.51) |
| AUCrofNO/AUCrof | NA | NA | NA | 10.8 | 23.1 | NA |
*
Geometric mean (68% range).
†
tmax: median (min.–max.). NA, not applicable.
‡
Point estimate and 90% CI exceeding the predefined equivalence acceptance range of 0.8 to 1.25; P > 0.05 (two one-sided t-tests).