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Reduced Plasma Nisoldipine Concentrations in Phenytoin‐Treated Patients with Epilepsy
Author(s) -
Michelucci R.,
Cipolla G.,
Passarelli D.,
Gatti G.,
Ochan M.,
Heinig R.,
Tassinari C. A.,
Perucca E.
Publication year - 1996
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1996.tb01032.x
Subject(s) - nisoldipine , phenytoin , pharmacokinetics , epilepsy , medicine , pharmacology , anesthesia , nifedipine , calcium , psychiatry
Summary: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 μg/L/h (95% confidence intervals, 0.6–3.8 μg/L/h) in the patients compared with 15.2 (10.7–21.6) μg/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. Key Words: Epilepsy‐ Nisoldipine‐Phenytoin‐Pharmacokinetics‐Drug interaction.