Pharmacodynamic and pharmacokinetic profile of S 17092, a new orally active prolyl endopeptidase inhibitor, in elderly healthy volunteers. A phase I study

摘要: Aims  The aim of this study was to characterize the pharmacodynamics and pharmacokinetics S 17092, a new orally active prolyl endopeptidase inhibitor following single repeated administration in elderly healthy volunteers. Methods  This double-blind, randomized, placebo-controlled, multiple dose male female volunteers (n = 36). Four doses were investigated sequential order: 100, 400, 800 1200 mg. Each administered once day then, after 1 week washout period, during 7 days. Pharmacodynamics assessed by measurement plasmatic (PEP) activity, quantitative electroencephalogram (EEG) psychometric tests. 17092 concentrations plasma quantified high performance liquid chromatography with tandem mass spectrometric detection. Results  PEP activity dose-dependently inhibited both 17092. mean maximal inhibition obtained within 0.5–2 h dosing, while lasted at least 12 h administration. appeared be centrally substance as it induced statistically significant modifications EEG compared placebo. 100 mg exerted an acute increase alpha band 4 h 8 h postdosing. When repeatedly over 7 days did not appear induce lasting central nervous system (CNS) effects. In tests, response times numeric working memory significantly reduced placebo, 800 mg dose. There some beneficial residual effects 1200 mg on 13: delayed word recall recognition sensitivity improved declines noted under Maximum measured concentration (Cmax) area curve (AUC) parameters increased proportion terminal half-life (t½) values ranged between 9 31 h 1 7 18 h 14. A interindividual variability observed all levels. well tolerated no clinically changes laboratory or physical any dose. Conclusions  17092 had potent, dose-dependent inhibitory effect PEP, two verbal tests there disruption vigilance task. results subjects indicated that is suitable for once-daily dosing without serious adverse events.