PHARMACOKINETICS AND ELECTROENCEPHALOGRAPHIC EFFECTS OF DARODIPINE 50-200 MG MODIFIED RELEASE (MR) ACUTE ORAL-ADMINISTRATION - DOSE-FINDINGSTUDY IN HEALTHY-VOLUNTEERS

Pharmacokinetics and electroencephalographic [EEG; power spectral anal ysis] effects of the acute oral Ca-antagonist darodipine (50mg MR, 100 mg MR, and 200mg MR) were investigated in a cross-over, placebo-contro lled study on healthy male volunteers (age 23-28 yrs). No effects on h eart rate, blood pressure or behaviour were observed with these doses at average. Cmax levels ranging between 4.74 and 33.53 ng/ml and with a Tmax ranging from 2 to 6h depending on the dose. No significant diff erences in drug kinetics were kinetics were observed between the 100-m g and the 200-mg dose. A significant increase of EEG total power and d ecrease of relative power in the 14.5-32.0 Hz frequency interval were observed at the 100-mg and 200-mg closes. These effects were great and more consistent across subjects at 100mg than at 200mg, and were corr elated with darodipine plasma concentrations, with indications of an a ctive concentration threshold at approximately 4-5 ng/ml. The 50-mg do se proved ineffective on EEG signal.