Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients.

1. The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2. Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven-fold (P less than 0.01) in patients taking enzyme-inducing anticonvulsants and increased by about 50% (P less than 0.05) in patients taking sodium valproate. 3. Nimodipine half-lives were shorter in enzyme-induced patients than in controls (3.9 +/- 2.0 h vs 9.1 +/- 3.4 h, means +/- s.d., P less than 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate-treated patients, half-lives (8.2 +/- 1.8 h) were similar to those found in controls.

Nimodipine in acute ischemic stroke: a double-blind controlled study.

Nimodipine (BAY e 9736), a new dihydropyridine derivative, has been shown to reduce neurological deficits and mortality induced by acute cerebral ischemia in experimental studies. We investigated the effects of this calcium antagonist in patients with acute ischemic stroke through a randomized, double-blind, parallel-designed trial in which nimodipine was compared with placebo. Forty-one of 54 screened cases were found to fulfil the inclusion criteria (sudden occurrence of a focal neurological deficit secondary to an acute ischemic event in the carotid area diagnosed after a complete neurological work-up) and entered the study. Nineteen of them were treated with nimodipine (40 mg t.i.d. administered for 28 days) and the remaining 22 with placebo, given in identical tablets. In all patients the treatment started within 12 h after the onset of the symptoms. Course and intensity of the neurological deficit were evaluated by the Mathew Scale (slightly modified). Forty patients concluded the trial. Nimodipine was withdrawn in one case following the occurrence of a skin rash whose causative relation with the test drug could not be clarified. Altogether, however, nimodipine was well tolerated and no severe cardiovascular adverse reactions were observed. In terms of efficacy, the scores obtained by the Mathew Scale showed a higher rate of improvement on nimodipine than on placebo, thus indicating that patients receiving the latter drug did not fare as well as those receiving the test medication. Our data suggest that nimodipine may be beneficial in the treatment of acute stroke.

EEG and clinical findings during pemoline treatment in children and adults with attention deficit disorder. An 8-week open trial.

A clinical study has been conducted on a selected group of 9 children and 12 adults with attention deficit disorder, evaluating the response to the therapy with magnesium pemoline by means of EEG power spectra. Pemoline was given orally in increasing doses ranging from 20 to 80 mg/day. EEG was recorded during baseline and at three fixed intervals during the treatment. Clinical response was assessed by objective and subjective ratings. In the adult sample, the drug produced two opposite patterns of EEG response which allowed us to discriminate by the 1st day of treatment responders who reported a paradoxical calming and non-responders who reported a worsening in anxiety. Inconsistent EEG power changes produced by the drug in children did not allow the discrimination of responders and non-responders. Children did not show paradoxical signs of sedation. EEG and clinical data suggest that adults and children show different drug response and that the paradoxical sedation is present only in adults.