REDUCED PLASMA NISOLDIPINE CONCENTRATIONS IN PHENYTOIN-TREATED PATIENTS WITH EPILEPSY

Purpose: To assess whether phenytoin affects the pharmacokinetics of t he dihydropyridine calcium antagonist nisoldipine. Methods. Twelve pat ients with epilepsy receiving chronic phenytoin therapy and 12 healthy control subjects matched for age and gender received a single oral do se of nisoldipine (40 and 20 mg, respectively). Blood samples were col lected for up to 48 h for estimation of plasma nisoldipine levels by c apillary gas chromatography. Results: Mean plasma nisoldipine concentr ations were much lower in the patients. Geometric means for areas unde r 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 increase s the first-pass metabolism of nisoldipine to a clinically important e xtent. In view of the magnitude and variability of interaction, use of nisoldipine in patients receiving chronic phenytoin therapy is contra indicated.