Table 3. Plasma pharmacokinetic parameters for cycle 1 day 1 and cycle 1 day 15 for the intensive pharmacokinetic sampling scheme.
|
Dose-escalation phase |
Expansion phase |
|||||||
|---|---|---|---|---|---|---|---|---|
| Cycle | Day | Parameter | 30 mg BID (n=4) | 45 mg BID (n=4) | 60 mg BID (n=7) | 80 mg BID (n=4) | Biliary 60 mg BID (n=7) | Total (N=26) |
| 1 | 1 | AUC0–8, h*ng ml−1a | 1000 (34.0) | 964 (28.4) | 1710 (23.9) | 2220 (78.9) | 1090 (293) | NR |
| Cmax, ng ml−1a | 327 (28.6) | 241 (43.2) | 545 (32.3) | 687 (66.6) | 365 (141) | NR | ||
| tmax, hb | 1.51 (1.00–4.07) | 2.53 (1.50–3.02) | 1.00 (0.500–4.08) | 2.02 (1.00–10.0) | 1.50 (1.13–10.0) | 1.50 (0.500–10.0) | ||
| 1 | 15 | AUC0-8, h*ng ml−1a | NA (NA) | 1490 (NC) | 1820 (14.4) | NA (NA) | 3760 (NC) | NR |
| Cmax, ng ml−1a | 417 (39.9) | 273 (64.7) | 512 (30.8) | NA (NA) | 594 (68.8) | NR | ||
| RAUCa | NA (NA) | 1.50 (NC) | 1.17 (18.4) | NA (NA) | 2.50 (NC) | 1.44 (32.8) | ||
| tmax, hb | 1.50 (1.50–3.83) | 2.00 (1.07–2.87) | 3.00 (0.533–7.12) | NA (NA) | 1.50 (1.00–7.02) | 1.50 (0.533–7.12) | ||
Abbreviations: AUC=area under the plasma concentration-time curve; AUC0–8=AUC from time 0 to 8 h; BID = twice daily; Cmax=first maximum observed plasma concentration; CV=coefficient of variation; NA=not applicable; NC=not calculated; NR=not reportable; RAUC=accumulation ratios.
a
Geometric mean (% CV).
b
Median (minimum–maximum).