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 < 0.01) in patients taking enzyme-inducing anticonvulsants and increased by about 50% (P < 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 < 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.