Acta Neurologica Scandinavica. 97(4):244-250, APRIL 1998
PMID: 9576639
Issn Print: 0001-6314
Publication Date: April 1998
Dose-dependent CSF acetylcholinesterase inhibition by SDZ ENA 713 in Alzheimer's disease
N. Cutler;R. Polinsky;J. Sramek;A. Enz;S. Jhee;L. Mancione;J. Hourani;P. Zolnouni;
+ Author Information
1California Clinical Trials, Beverly Hills, CA 90211, USA; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
Abstract
This study evaluates the activity of SDZ ENA 713, a centrally-selective acetylcholinesterase (AChE) inhibitor, in the cerebral spinal fluid (CSF) of patients with Alzheimer's disease (AD), and its relationship to central and peripheral pharmacokinetic parameters.Eighteen AD patients were enrolled in this open-label, multiple-dose study. Patients were titrated in 1 mg bid/week increments to target doses of 1, 2, 3, 4, 5, or 6 mg bid SDZ ENA 713. After patients had been maintained at their target dose for at least 3 days, continuous CSF samples were obtained via a lumbar catheter for 12.5 h, beginning 0.5 h prior to the final dose of SDZ ENA 713.Dose-dependent inhibition of CSF AChE was significantly correlated (P<0.05) with plasma drug and metabolite concentrations. The 6 mg bid treatment group showed a maximum mean inhibition of 62% at 5.6 h post-dose.Rapid, sustained, dose-dependent inhibition of CSF AChE suggests that SDZ ENA 713 has therapeutic potential in AD patients.
