DOSE-DEPENDENT CSF ACETYLCHOLINESTERASE INHIBITION BY SDZ-ENA-713 IN ALZHEIMERS-DISEASE

Introduction - This study evaluates the activity of SDZ ENA 713, a cen trally selective acetylcholinesterase (AChE) inhibitor, in the cerebra l spinal fluid (CSF) of patients with Alzheimer's disease (AD), and it s relationship to central and peripheral pharmacokinetic parameters. M ethods - Eighteen AD patients were enrolled in this open-label, multip le-dose study. Patients were titrated in 1 mg bid/week increments to t arget 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, continuo us CSF samples were obtained via a lumbar catheter for 12.5 h, beginni ng 0.5 h prior to the final dose of SDZ ENA 713. Results - Dose-depend ent inhibition of CSF AChE was significantly correlated (P<0.05) with plasma drug and metabolite concentrations, The 6 mg bid treatment grou p showed a maximum mean inhibition of 62% at 5.6 h post-dose. Conclusi on - Rapid, sustained, dose-dependent inhibition of CSF AChE suggests that SDZ ENA 713 has therapeutic potential in AD patients.