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Table 3 Noncompartmental pharmacokinetics in cerebrospinal fluid by dose following single dosing with GSK933776 a

From: Modulation of β-amyloid by a single dose of GSK933776 in patients with mild Alzheimer’s disease: a phase I study

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)

  1. 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.
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Alzheimer's Research & Therapy

ISSN: 1758-9193