Table 2.
Pharmacokinetic parameters of riociguat and M1 by age and sex following a single oral dose of riociguat 2.5 mg in the healthy volunteer study
| Female | Male | |||
|---|---|---|---|---|
| Parameter | Young (n = 9) | Elderly (n = 9) | Young (n = 9) | Elderly (n = 9) |
| Riociguat | ||||
| AUC, μg h/L | 803 (55) | 1,145 (36) | 750 (58) | 1,036 (48) |
| Cmax, μg/L | 113.0 (22) | 125.0 (35) | 80.4 (25) | 96.7 (32) |
| AUCnorm, g h/L | 24.8 (57) | 32.6 (45) | 26.5 (55) | 32.8 (50) |
| Cmax,norm, g/L | 3.48 (20) | 3.56 (36) | 2.84 (23) | 3.06 (22) |
| t1/2, hours | 8.97 (51) | 11.80 (31) | 8.10 (39) | 12.20 (62) |
| tmax, hours, median (range) | 1.5 (1.0–2.0) | 2.0 (1.0–2.5) | 1.5 (1.0–3.0) | 2.0 (1.0–3.0) |
| CLR, L/ha | 0.320 (28.1) | 0.223 (33.3) | 0.389 (36.6) | 0.287 (28.1) |
| Aeur(0–72), %a | 11.1 (45.6) | 11.1 (59.1) | 12.0 (44.0) | 12.8 (49.7) |
| M1 | ||||
| AUC, μg h/L | 640 (26) | 651 (38) | 476 (20) | 687 (44) |
| Cmax, μg/L | 28.1 (53) | 22.4 (52) | 14.9 (44) | 18.8 (71) |
| AUCnorm, g h/L | 20.5 (26) | 19.2 (30) | 17.4 (28) | 22.5 (35) |
| Cmax,norm, g/L | 0.90 (51) | 0.661 (42) | 0.544 (51) | 0.615 (65) |
| t1/2, hours | 16.0 (34) | 16.7 (21) | 14.9 (28) | 21.3 (33) |
| tmax, hours, median (range) | 3.0 (2.5–10) | 8.0 (2.5–16) | 10.0 (2.5–24) | 10.0 (8.0–24) |
| CLR, L/ha | 0.824 (31.8) | 0.487 (36.4) | 0.718 (39.2) | 0.573 (44.0) |
| Aeur(0–72), %a | 22.4 (41) | 14.1 (51) | 14.5 (44) | 17.8 (75) |
Note
Unless otherwise stated, data are expressed as geometric means (percentage coefficient of variation). Aeur(0–72): proportion of dose excreted into urine from time 0 to 72 hours; AUC: area under the plasma concentration–time curve; AUCnorm: AUC divided by dose per kilogram of body weight; CLR: renal clearance; Cmax: maximum concentration in plasma; Cmax,norm: Cmax divided by dose per kilogram of body weight; t1/2: terminal elimination half-life; tmax: time to Cmax.
a
Arithmetic mean (percentage coefficient of variation).