Pharmacokinetic measurements
In each treatment period, for the determination of plasma concentrations of zamicastat and its metabolites, venous blood samples (6 mL) were drawn into lithium heparin tubes, 30 minutes after breakfast on day -1 and at pre-dose (within 10 minutes) on days 3, 6, 8, and 10. Plasma concentrations of zamicastat and its metabolites BIA 5-453 and BIA 5-961 were determined by SYNLAB Analytics & Services Switzerland AG (Sternenfeldstrasse 14 CH-4127 Birsfelden, Switzerland), in accordance with the applicable principles of GLP, using a previously validated LC-MS/MS analytical method.
The pharmacokinetics analysis set (PK population) included all subjects who had received at least one dose of zamicastat without major protocol deviation and had at least one valid evaluable post-dose plasma zamicastat concentration.