Table 4.
Summary of PK parameters in plasma (N=9)
| Parameter | Torasemide-IR | Furosemide-IR | Torasemide-PR |
|---|---|---|---|
| Cmax (ng/mL) | |||
| Arithmetic mean (SD) | 1,252.5 (299.7) | 1,039.9 (415.4) | 807.1 (138.8) |
| Median (min–max) | 1,257.9 (846.1–1781.5) | 922.6 (508.3–1903.4) | 826.7 (558.8–975.5) |
| P-value | |||
| Torasemide-IR | – | 0.262 | 0.002 |
| Furosemide-IR | – | – | 0.313 |
| Torasemide-PR | – | – | – |
| tmax (h) | |||
| Arithmetic mean (SD) | 1.0 (0.4) | 1.6 (0.8) | 1.8 (0.4) |
| Median (min–max) | 1.0 (0.5–1.7) | 1.5 (1–3.5) | 1.7 (1.2–2.5) |
| P-value | |||
| Torasemide-IR | – | 0.028 | 0.012 |
| Furosemide-IR | – | – | 0.246 |
| Torasemide-PR | – | – | – |
| AUC0−t (ng h/mL) | |||
| Arithmetic mean (SD) | 3,976.3 (1277.0) | 3,540.9 (776.6) | 4,362.1 (1386.5) |
| Median (min–max) | 4,050.15 (2131.9–5875.0) | 3,753.2 (2119.5–4528.2) | 4,188.0 (2616.9–6907.7) |
| P-value | |||
| Torasemide-IR | – | 0.321 | 0.031 |
| Furosemide-IR | – | – | 0.091 |
| Torasemide-PR | – | – | – |
| AUC0−∞ (ng h/mL) | |||
| Arithmetic mean (SD) | 4,096.4 (1386.8) | 3,761.1 (852.4) | 4,496.8 (1516.7) |
| Median (min–max) | 4,200.3 (2154.2–6255.3) | 3,896.4 (2244.6–4764.9) | 4,252.5 (2648.4–7396.7) |
| P-value | |||
| Torasemide-IR | – | 0.674 | 0.041 |
| Furosemide-IR | – | – | 0.231 |
| Torasemide-PR | – | – | – |
| Ke (L/h) | |||
| Arithmetic mean (SD) | 0.14 (0.02) | 0.32 (0.13) | 0.15 (0.02) |
| Median (min–max) | 0.15 (0.11–0.17) | 0.34 (0.14–0.52) | 0.16 (0.11–0.17) |
| P-value | |||
| Torasemide-IR | – | 0.014 | 0.425 |
| Furosemide-IR | – | – | 0.021 |
| Torasemide-PR | – | – | – |
| t1/2 (h) | |||
| Arithmetic mean (SD) | 4.92 (0.77) | 2.65 (1.32) | 4.65 (0.80) |
| Median (min–max) | 4.60 (4.01–6.17) | 2.01 (1.32–4.73) | 4.39 (3.94–6.55) |
| P-value | |||
| Torasemide-IR | – | 0.004 | 0.499 |
| Furosemide-IR | – | – | 0.019 |
| Torasemide-PR | – | – | – |
| Vd/F (L) | |||
| Arithmetic mean (SD) | 18.5 (4.8) | 41.4 (19.0) | 15.9 (3.9) |
| Median (min–max) | 16.2 (13.8–28.8) | 42.3 (19.5–77.8) | 15.4 (10.1–22.3) |
| P-value | |||
| Torasemide-IR | – | 0.023 | 0.014 |
| Furosemide-IR | – | – | 0.015 |
| Torasemide-PR | – | – | – |
| Cl/F (L/h) | |||
| Arithmetic mean (SD) | 2.7 (0.98) | 11.2 (3.1) | 2.4 (0.8) |
| Median (min–max) | 2.4 (1.6–4.6) | 10.3 (8.4–17.8) | 2.3 (1.3–3.8) |
| P-value | |||
| Torasemide-IR | – | <0.0001 | 0.046 |
| Furosemide-IR | – | – | <0.0001 |
| Torasemide-PR | – | – | – |
| MRT (h) | |||
| Arithmetic mean (SD) | 4.5 (1.0) | 3.8 (1.1) | 5.4 (0.9) |
| Median (min–max) | 4.5 (3.2–6.3) | 3.6 (2.5–5.9) | 5.5 (4.2–6.8) |
| P-value | |||
| Torasemide-IR | – | 0.243 | <0.0001 |
| Furosemide-IR | – | – | 0.008 |
| Torasemide-PR | – | – | – |
Notes: Data are mean (SD) and median (min-max) for every pharmacokinetic parameter. Significance for parameters was tested by means of a one-way analysis of variance (ANOVA) followed by a post hoc analysis to assess differences by pairs. Bold values indicate statistical significance.
Abbreviations: AUC, area under the curve; Cmax, maximum plasma concentration; Cl/F, clearance; h, hours; Ke, elimination rate constant; max, maximum; min, minimum; MRT, mean residence time; PK, pharmacokinetic; IR, immediate-release; PR, prolonged release; tmax, time to reach Cmax; t1/2, elimination half-life; Vd/F, volume of distribution; SD, standard deviation.