Table 2.
Summary of Pharmacokinetic Parameters of Midazolam and Its Metabolites Administered With and Without Tenapanor in Healthy Volunteers
| Parameter (Units) | Statistic | Midazolam (N = 28) | Midazolam + Tenapanor (N = 26) | Ratioa (90%CI), % |
|---|---|---|---|---|
| Midazolam | ||||
| AUC (ng·h/mL) | n | 27 | 26 | |
| Arithmetic mean (SD) | 96.2 (28.3) | 103 (30.9) | ||
| Geometric mean (GCV%) | 92.5 (29.2) | 98.5 (28.8) | 107 (101‐113) | |
| AUC0‐t (ng·h/mL) | n | 28 | 26 | |
| Arithmetic mean (SD) | 101 (51.2) | 98.9 (28.9) | ||
| Geometric mean (GCV%) | 93.9 (37.9) | 95.2 (28.2) | 106 (100‐113) | |
| Cmax (ng/mL) | n | 28 | 26 | |
| Arithmetic mean (SD) | 39.5 (15.4) | 40.8 (14.2) | ||
| Geometric mean (GCV%) | 36.8 (40.7) | 38.3 (38.4) | 104 (89.6‐122) | |
| tmax (h) | n | 28 | 26 | |
| Median (range) | 0.50 (0.25‐0.55) | 0.50 (0.25‐0.55) | ||
| t1/2 (h) | n | 28 | 26 | |
| Arithmetic mean (SD) | 5.43 (1.90) | 5.53 (1.49) | ||
| Geometric mean (GCV%) | 5.15 (34.4) | 5.33 (28.5) | ||
| 1‐OH‐midazolam | ||||
| AUC (ng·h/mL) | n | 28 | 25 | |
| Arithmetic mean (SD) | 54.1 (31.6) | 60.6 (32.9) | ||
| Geometric mean (GCV%) | 48.8 (43.6) | 55.0 (43.5) | 110 (103‐116) | |
| AUC0‐t (ng·h/mL) | n | 28 | 26 | |
| Arithmetic mean (SD) | 52.1 (29.7) | 58.2 (31.9) | ||
| Geometric mean (GCV%) | 47.2 (43.1) | 52.7 (43.8) | 110 (104‐116) | |
| Cmax (ng/mL) | n | 28 | 26 | |
| Arithmetic mean (SD) | 26.6 (12.0) | 28.0 (12.9) | ||
| Geometric mean (GCV%) | 24.1 (47.8) | 25.2 (51.3) | 103 (87.2‐122) | |
| tmax (h) | n | 28 | 26 | |
| Median (range) | 0.50 (0.25‐0.55) | 0.50 (0.25‐0.55) | ||
| t1/2 (h) | n | 28 | 25 | |
| Arithmetic mean (SD) | 5.14 (2.22) | 5.01 (1.66) | ||
| Geometric mean (GCV%) | 4.64 (50.0) | 4.73 (37.1) | ||
| 4‐OH‐midazolam | ||||
| AUC (ng·h/mL) | n | 28 | 26 | |
| Arithmetic mean (SD) | 6.14 (1.56) | 6.32 (1.54) | ||
| Geometric mean (GCV%) | 5.96 (25.3) | 6.14 (24.3) | 105 (98.7‐111) | |
| AUC0‐t (ng·h/mL) | n | 28 | 26 | |
| Arithmetic mean (SD) | 5.65 (1.50) | 5.87 (1.47) | ||
| Geometric mean (GCV%) | 5.47 (26.9) | 5.69 (25.3) | 106 (99.1‐113) | |
| Cmax (ng/mL) | n | 28 | 26 | |
| Arithmetic mean (SD) | 2.11 (0.757) | 2.20 (0.649) | ||
| Geometric mean (GCV%) | 1.99 (37.6) | 2.10 (33.8) | 105 (90.5‐122) | |
| tmax (h) | n | 28 | 26 | |
| Median (range) | 0.50 (0.25‐1.02) | 0.50 (0.25‐2.00) | ||
| t1/2 (h) | n | 28 | 26 | |
| Arithmetic mean (SD) | 2.48 (0.820) | 2.36 (0.581) | ||
| Geometric mean (GCV%) | 2.37 (30.2) | 2.30 (22.0) |
AUC, area under the plasma concentration‐time curve from 0 to infinity; AUC0‐t, area under the plasma concentration‐time curve from 0 (predose) to the last quantifiable concentration; Cmax, maximum observed concentration in plasma; GCV%, geometric coefficient of variation; tmax, time to Cmax; t1/2, apparent terminal half‐life.
a
Ratio is (midazolam + tenapanor)/tenapanor, based on geometric least‐squares means.