Table 4.
Mean estimates and 95% confidence intervals for pharmacokinetic-pharmacodynamic model parameters obtained for cisapride, d,l-sotalol and moxifloxacin after administration of different doses to conscious dogs and healthy subjects
| Parameters | Cisapride | |
|---|---|---|
| Dogs (n = 7) | Healthy subjects (n = 24) | |
| QT0 (ms) | 238 (237, 240) | 386 (382, 390) |
| α | 0.26 (0.20, 0.33) | 0.18 (0.14, 0.23) |
| A (ms) | 5.6 (3.9, 8.1) | 3.3 (1.1, 5.95) |
| φ (h) | 19.9 (15.8, 25.8) | 4.3 (2.4, 8.68) |
| Slope (ms/nm) | 0.0045 (0.00096, 0.0098) | 0.09 (0.087, 0.12) |
| BSV (QT0) % | 6.48 (6.46-6.49) | 2.23 (1.75, 3.01) |
| BSV (α) % | 89 (47, 190) | 17.31 (11.48, 26.95) |
| BSV (A) % | 7.14 (5.32, 10.93) | 6.52 (3.73, 14.57) |
| BSV (φ) % | 7.08 (4.40, 13.13) | 19.04 (11.79, 35.3) |
| BSV (Slope) % | 105 (66, 180) | 48.2 (21.94, 93.5) |
| Residual error (ms) | 5.8 (5.7, 5.9) | 11.66 (11.13, 13.04) |
| Prob effect ≥10 ms at Cmax | 0.75 | 1.0 |
| Cmax (nm) | 2808 | 936 |
| Parameters | d,l-sotalol | |
|---|---|---|
| Dogs s (n = 5) | Healthy subjects (n = 30) | |
| QT0 (ms) | 255 (253, 257) | 387 (383, 392) |
| α | 0.18 (0.11, 0.3) | 0.27 (0.24, 0.3) |
| A (ms) | 6.58 (2.09, 19.78) | 3.3 (2.4, 4.29) |
| φ (h) | 12.15 (6.51, 35.77) | 6.22 (5.05, 7.58) |
| Slope (ms/nm) | 0.002 (0.0006, 0.008) | 0.021 (0.017, 0.026) |
| BSV (QT0) % | 6.25 (6.23, 6.28) | 5.08 (5.05, 5.11) |
| BSV (α) % | 137 (55, 410) | 80 (54, 123) |
| BSV (A) % | 11.02 (8.9, 17.3) | 6.38 (4.08, 10.15) |
| BSV (φ) % | 11.11 (4.73, 30.70) | 13.98 (8.44, 24.24) |
| BSV (Slope) % | 36.8 (22.6, 71.1) | 49.7 (18.2, 108) |
| Residual error (ms) | 9.0 (8.8, 9.3) | 5.9 (5.68, 6.14) |
| Prob effect ≥10 ms at Cmax | 0.9 | 1.0 |
| Cmax (nm) | 22 310 | 5605 |
| Parameters | Moxifloxacin | |
|---|---|---|
| Dogs (n = 8) | Healthy subjects (n = 137) | |
| QT0 (ms) | 240 (238, 242) | 399 (394, 403) |
| α | 0.28 (0.22, 0.35) | 0.40 (0.38, 0.42) |
| A (ms) | 4.6 (3.1, 7.0) | 2.4 (1.7, 2.9) |
| φ (h) | 23.1 (15.1, 34.6) | 10.0 (7.3, 12.9) |
| Slope (ms/nm) | 0.00056 (0.00002, 0.0014) | 0.0039 (0.0033, 0.0044) |
| BSV (QT0) % | 6.46 (6.43, 6.48) | 5.01 (4.98, 5.04) |
| BSV (α) % | 86 (48, 177) | 41 (33, 52) |
| BSV (A) % | 9.8 (7.4, 14.8) | 5.3 (3.6, 8.0) |
| BSV (φ) % | 13 (8, 23) | 18 (10, 31) |
| BSV (Slope) % | 25 (17, 39) | 41 (29, 53) |
| Residual error (ms) | 9.4 (9.3, 9.5) | 5.3 (5.2, 5.4) |
| Prob effect ≥10 ms at Cmax | 1.0 | 1.0 |
| Cmax (nm) | 112 930 | 10 300 |
QT0 (ms) is the intercept of the QT–RR relationship; RR (s) is the interval between successive R waves, α is the individual heart rate correction factor, A (ms) is the amplitude of circadian rhythm, φ (h) is the phase of the cosine function, slope 9ms/concentration) is the linear pharmacodynamic relationship; BSV = between subject variability.