TABLE 1.
Steady-state intracellular CBV-TP PK parameters, by treatment and gender, and comparison
| Intracellular CBV-TP PK parameter | Geometric mean (% CV)
|
Geometric least square mean ratio (90% CI)
|
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Treatment A (ABC 300 mg BID regimen)
|
Treatment B (ABC 600 mg QD regimen)
|
|||||||||
| All subjects (n = 27) | Male (n = 18) | Female (n = 9) | All subjects (n = 27) | Male (n = 18) | Female (n = 9) | Treatment B/A (n = 27/27) | Female/male (n = 9/18)
|
|||
| Treatment A | Treatment B | Combinedc | ||||||||
| Original scale | ||||||||||
| AUC0-24(h·fmol/million cells)a | 814 (64) | 688 (53) | 1,138 (72) | 1,051 (71) | 792 (45) | 1,851 (69) | 1.32 (1.07, 1.63) | 1.76 (1.27, 2.45) | 2.21 (1.63, 2.99) | 2.09 (1.69, 2.58) |
| Cmax (fmol/million cells) | 58.5 (54) | 49.3 (49) | 82.5 (42) | 114 (76) | 86.5 (49) | 198 (83) | 1.99 (1.61, 2.45) | 1.76 (1.33, 2.32) | 2.16 (1.52, 3.07) | 2.05 (1.64, 2.57) |
| Cτ (fmol/million cells) | 23.5 (102) | 18.7 (98) | 37.2 (84) | 27.1 (137) | 20.0 (109) | 49.9 (148) | 1.18 (0.82, 1.71) | 2.05 (1.17, 3.59) | 2.21 (1.27, 3.84) | 2.13 (1.36, 3.35) |
| AUCCBV/AUCABCd | 103 (66) | 102 (69) | 105 (66) | 123 (65) | 109 (58) | 158 (74) | 1.22 (0.96, 1.55) | NAe | NA | 1.24 (0.96, 1.62) |
| Wt normalizedb | ||||||||||
| AUC0-24(h·fmol/million cells)1 | 811 (61) | 719 (46) | 1,034 (82) | 1,048 (74) | 827 (57) | 1,683 (74) | 1.32 (1.07, 1.63) | 1.53 (1.09, 2.14) | 1.92 (1.34, 2.74) | 1.81 (1.41, 2.34) |
| Cmax (fmol/million cells) | 58.3 (49) | 51.4 (43) | 75.0 (50) | 114 (76) | 90.3 (62) | 180 (88) | 1.99 (1.58, 2.49) | 1.53 (1.16, 2.01) | 1.87 (1.25, 2.81) | 1.78 (1.35, 2.35) |
| Cτ (fmol/million cells) | 23.4 (98) | 19.5 (91) | 33.8 (99) | 27.1 (136) | 20.9 (113) | 45.3 (152) | 1.18 (0.82, 1.71) | 1.78 (1.01, 3.12) | 1.92 (1.09, 3.36) | 1.85 (1.17, 2.92) |
a
AUC0-24for BID regimen was calculated as 2 × AUC(0 − τ).
b
Weight-normalized PK parameters were calculated as PK × weight (kg)/70 (kg).
c
Average of treatments A and B for each subject was used.
d
Ratio of CBV-TP AUC0-24and ABC AUC0-24, expressed as (fmol·h/million cells)/(μg·h/ml).
e
NA, not available.