Pharmacokinetic Profile of Orally Administered Scyllo-Inositol (Elnd005) in Plasma, Cerebrospinal Fluid and Brain, and Corresponding Effect on Amyloid-Beta in Healthy Subjects.
ELND005 (scyllo-inositol), an endogenous inositol stereoisomer, is being investigated as an oral treatment for Alzheimer's disease (AD). Pharmacokinetics of ELND005 in plasma, cerebrospinal fluid (CSF), and brain was characterized in healthy young subjects. Eight men received 2000 mg ELND005 every 12 hours for 10 days. Plasma and CSF samples were collected at predetermined time points; ELND005 and amyloid-beta (Aβ) fragments were measured by validated bioanalytical methods. Brain ELND005 levels, estimated by (1) H Magnetic Resonance Spectroscopy (MRS) scans were obtained from gray/white matter voxels at baseline and Day 8. ELND005 was well-tolerated during the study. During the apparent steady state, ELND005 plasma levels rapidly peaked at 39.8 µg/mL and decreased to an average trough concentration of 10.6 µg/mL at the end of the 12-hour dosing regimen. In contrast, CSF drug levels slowly peaked at 13.7 µg/mL and remained near the same level with average trough concentrations of 12.4 µg/mL. At Day 8, Brain ELND005 concentrations increased by 58-76% compared to baseline levels. The CSF concentrations achieved in this study were similar to those associated with efficacy in transgenic models of AD. No changes were detected in plasma and CSF levels of Aβ fragments.
Elan Pharmaceuticals, Inc., South San Francisco, CA, USA.
Earvin
E
Liang
Elan Pharmaceuticals, Inc., South San Francisco, CA, USA.
Pamela
P
Garzone
Elan Pharmaceuticals, Inc., South San Francisco, CA, USA.
Jesse M
JM
Cedarbaum
Elan Pharmaceuticals, Inc., South San Francisco, CA, USA.
Martin
M
Koller
Huntington Medical Research Institutes, Pasadena, CA, USA.
Thao
T
Tran
Huntington Medical Research Institutes, Pasadena, CA, USA.
Victor
V
Xu
Huntington Medical Research Institutes, Pasadena, CA, USA.
Brian
B
Ross
PAREXEL International Early Phase (formerly California Clinical Trials), Glendale, CA, USA.
Stanford S
SS
Jhee
The University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Larry
L
Ereshefsky
Transition Therapeutics, Toronto, ON, Canada.
Aleksandra
A
Pastrak
Elan Pharmaceuticals, Inc., South San Francisco, CA, USA.
Susan
S
Abushakra
ELND005; MRS; beta amyloid; brain; scyllo-inositol