Related Experiment Videos
Reduced plasma nisoldipine concentrations in phenytoin-treated patients with epilepsy
R Michelucci1, G Cipolla, D Passarelli
1Department of Neurology, Bellaria University Hospital, Bologna, Italy.
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 (AUC0-tn) normalized to a 20-mg dose were 1.6 micrograms/L/h (95% confidence intervals, 0.6-3.8 micrograms/L/h) in the patients compared with 15.2 (10.7-21.6) micrograms/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.