TABLE 3.
Levels of BMS 181184 in tissues after multiple dosing over 16 days
| Drug dose (mg/kg · day) | BMS 181184 level (mean ± SEM) ina:
|
||||||
|---|---|---|---|---|---|---|---|
| Brain (μg/g) | CSF (μg/ml) | Vitreous fluid (μg/ml) | Lung (μg/g) | Liver (μg/g) | Spleen (μg/g) | Kidneyb (μg/g) | |
| 10 | 4.30 ± 0.72 [0.0052] | NDc | 2.84 ± 0.28 [0.0034] | 28.18 ± 0.90 [0.0345] | 30.37 ± 5.10 [0.0372] | 11.48 ± 0.55 [0.0140] | 37.45 ± 5.75 [0.0458] |
| 25 | 4.76 ± 0.81 [0.0036] | ND | 2.93 ± 0.35 [0.0022] | 38.09 ± 2.77 [0.0293] | 54.33 ± 2.19 [0.0418] | 17.52 ± 1.90 [0.0134] | 72.66 ± 3.39 [0.0559] |
| 50 | 6.55 ± 0.72 [0.0034] | 10.58 ± 1.00 [0.0056] | 3.67 ± 0.19 [0.0019] | 53.86 ± 5.19 [0.0287] | 64.02 ± 6.05 [0.0335] | 20.73 ± 1.02 [0.0108] | 142.4 ± 12.60 [0.0745] |
| 150 | 7.65 ± 0.89 [0.0055] | 4.06 ± 0.83 [0.0029] | 1.75 ± 0.24 [0.0012] | 41.31 ± 2.77 [0.0298] | 48.01 ± 4.38 [0.0346] | 20.93 ± 1.05 [0.0151] | 336.59 ± 17.98 [0.2430] |
a
Values in brackets are ratios of mean tissue levels to mean plasma AUC0–24s after multiple dosing.
b
P < 0.001 by Kruskal-Wallis nonparametric ANOVA.
c
ND, not determined.