Table 3.
Noncompartmental pharmacokinetics in cerebrospinal fluid by dose following single dosing with GSK933776 a
|
Parameters |
Median (range) |
||
|---|---|---|---|
| 1 mg/kg ( N /n = 6/3) | 3 mg/kg ( N /n = 6/6) | 6 mg/kg ( N /n = 6/4) | |
| AUC0–4 (h∙mg/ml) |
0.0 (0.0 to 71.1) |
0.0 (0.0 to 32.1) |
0.0 (0.0 to 38.9) |
| AUC5–12 (h∙mg/ml) |
87.9 (12.7 to 134.9) |
54.8 (6.3 to 398.8) |
140.2 (49.1 to 626.5) |
| AUC0–12 (h∙mg/ml) |
87.9 (12.7 to 210.9) |
54.8 (6.3 to 456.0) |
140.2 (49.1 to 703.9) |
| AUC0–t (h∙mg/ml) |
6.3 (0.0 to 339.5) |
54.8 (6.3 to 456.0) |
88.1 (0.0 to 703.9) |
|
Cmax (μg/ml) |
12.7 (0.0 to 47.8) |
20.1 (12.5 to 84.1) |
28.5 (0.0 to 116.9) |
|
Ct (μg/ml) |
19.0 (11.4 to 25.3) |
19.6 (12.5 to 84.1) |
47.9 (18.6 to 116.1) |
|
tmax (h) |
10.0 (2.0 to 11.0) |
11.8 (10.0 to 12.0) |
12.0 (11.0 to 12.0) |
|
tlast (h) |
17.0 (11.0 to 19.0) |
12.0 (11.6 to 12.0) |
12.0 (12 to 12) |
| tlag (h) | 8.0 (0.0 to 10.0) | 8.5 (2.0 to 11.0) | 5.0 (2.0 to 8.0) |
aAUC0–4: Area under the cerebrospinal fluid (CSF) concentration–time curve from time 0 to 4 hours postdosing; AUC0–12: Area under the CSF concentration–time curve from time 0 to 12 hours postdosing; AUC5–12: Area under the CSF concentration–time curve from 5 to 12 hours postdosing; AUC0–t: Area under the CSF concentration–time curve to the last quantifiable concentration; Cmax: Maximum CSF concentration; Ct: Concentration at tlast; N: Number of patients who received GSK933776; n: Number of patients from whom quantifiable CSF pharmacokinetics concentration levels were obtained and analysed; tlast: Time of the last observed CSF concentration; tmax: Time of occurrence of Cmax; tlag: Time prior to the first measurable (that is, nonzero) concentration in CSF.