Plasma concentration and CNS effects of Ca antagonists darodipine and nimodipine after single-dose oral administration to healthy volunteers

The dynamics at the brain level (quantitative EEG), plasma kinetics and eff ects on blood pressure and heart rate of the Ca antagonists, darodipine (sl ow-release, 50-200 mg) and nimodipine (30 mg), were compared in a double-bl ind cross-over study on healthy volunteers during a 9-hour period following single drug/placebo administration. Increased EEG total power was observed after 100 and 200 mg daropidine; a concomitant decrease of 14.5-32.0 Hz re lative power was observed at 100 mg. The 50-mg dose proved ineffective. The se effects were correlated with the darodipine plasma concentration only at the 100-mg dose, with indications of an active concentration interval at a pproximately 5-10 ng/ml; a reduction in diastolic blood pressure and increa sed heart rate proved to be linearly correlated with the drug plasma concen tration throughout the entire concentration range. Comparable EEG effects w ere observed after nimodipine, but they did not correlate with the plasma c oncentration. Implications of the predictability of the brain effect from t he drug plasma concentration and differential thresholds for the brain acti on and effects on (peripheral) circulation are suggested.