Pharmacokinetics and electroencephalographic effects of darodipine 50-200 mg modified release (MR) acute oral administration: dose-finding study in healthy volunteers.

ABSTRACT

Pharmacokinetics and electroencephalographic [EEG; power spectral analysis] effects of the acute oral Ca-antagonist darodipine (50 mg MR, 100 mg MR, and 200 mg MR) were investigated in a cross-over, placebo-controlled study on healthy male volunteers (age 23-28 yrs). No effects on heart 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 6 h depending on the dose. No significant differences in drug kinetics were observed between the 100-mg and the 200-mg dose. A significant increase of EEG total power and a decrease of relative power in the 14.5-32.0 Hz frequency interval were observed at the 100-mg and 200-mg doses. These effects were greater and more consistent across subjects at 100 mg than at 200 mg, and were correlated with darodipine plasma concentrations, with indications of an active concentration threshold at approximately 4-5 ng/ml. The 50-mg dose proved ineffective on the EEG signal.