Reduced plasma nisoldipine concentrations in phenytoin-treated patients with epilepsy

Purpose: To assess whether phenytoin affects the pharmacokinetics of the dihydropyridine calcium antagonist nisoldipine. Methods. Twelve patients with epilepsy receiving chronic phenytoin therapy and 12 healthy control subjects matched for age and gender received a single oral dose of nisoldipine (40 and 20 mg, respectively). Blood samples were collected for up to 48 h for estimation of plasma nisoldipine levels by capillary gas chromatography. Results: Mean plasma nisoldipine concentrations were much lower in the patients. Geometric means for areas under the concentration-time curve (AUC(0-tn)) normalized to a 20-mg dose were 1.6 mu g/L/h (95% confidence intervals, 0.6-3.8 mu g/L/h) in the patients compared with 15.2 (10.7-21.6) mu g/L/h in control subjects (p < 0.002). Conclusions: These results suggest that phenytoin increases the first-pass metabolism of nisoldipine to a clinically important extent. In view of the magnitude and variability of interaction, use of nisoldipine in patients receiving chronic phenytoin therapy is contraindicated.