Clinically observed and Simcyp [and GastroPlus] model-predicted pharmacokinetic parameters of panobinostat after a single oral dose
| PK Parameter | Study | Dose | |||||
|---|---|---|---|---|---|---|---|
| 15 mg | 20 mg | 30 mg | 40 mg | 60 mg | 80 mg | ||
| N | B2101 | 3 | 36 | 31 | 4 | ||
| B2102 | 9 | 18 | 24 | 53 | 18 | ||
| Simulated | 100 | 100 | 100 | 100 | 100 | 100 | |
| Cmax (ng/ml) | B2101 | 12.2 (65) | 23.6 (57) | 34.0 (56) | 55.4 (40) | ||
| B2102 | 19.5 (61) | 39.8 (69) | 58 (59) | 66.9 (70) | 63.5 (58) | ||
| Simulated | 14.6 (146) | 19.5 (146) [31]a | 29.2 (146) [47.5] | 39.1 (146) [58.9] | 58.8 (146) | 78.7 (146) | |
| PE (%)b | +20 | 0 to −17 [+31 to +59] | −27 to−-14 [+19 to +40] | -33 [+2] | −12 to +6 | +24 | |
| AUC0-48 ng × h/ml | B2101 | n/a | 198 (48) | 262 (49) | 390 (28) | ||
| B2102 | 131 (58) | 310 (117) | 299 (76) | 330 (62) | 342 (54) | ||
| Simulated | 96.5 (87) | 129 (87) [151] | 195 (88) [231] | 262 (88) [280] | 398 (88) | 538 (89) | |
| PE (%) | −2 to −35 [−24 to +15] | −37 to −26 [−25 to −12] | −12 [−6] | +2 to +21 | +57 | ||
| Tmaxc (h) | B2101 | 1 (0.5–2) | 1 (0.5–4.5) | 1 (0.5–8) | |||
| B2102 | 2.1 (0.5–3.1) | 1 (0.5–28) | 0.8 (0.5–3.1) | 1 (0.5–45.7) | 1 (0.5–6) | ||
| Simulated | 1.3 (0.3–1.8) | 1.3 (0.3–1.8) [1.28] | 1.3 (0.3–1.8) [1.28] | 1.3 (0.3–1.8) [1.28] | 1.3 (0.3–1.8) | 1.3 (0.3–1.8) | |
| PE (%) | +30 | −38 to +30 [−39 to +28] | +30 [+28] | +63 [+60] | +30 | +30 | |
n/a, not available.
↵a The simulated value in brackets is the predicted value and prediction error from GastroPlus of one simulated subject.
↵b PE, prediction error (%) = [(predicted-observed)/observed] × 100.
↵c Values are the median (range) for Tmax and arithmetic mean (CV%) for all other parameters.