Michelucci R, Cipolla G, Passarelli D, Gatti G, Ochan M, Heinig R, Tassinari C A, Perucca E
Department of Neurology, Bellaria University Hospital, Bologna, Italy.
Epilepsia. 1996 Nov;37(11):1107-10. doi: 10.1111/j.1528-1157.1996.tb01032.x.
To assess whether phenytoin affects the pharmacokinetics of the dihydropyridine calcium antagonist nisoldipine.
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.
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).
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.
评估苯妥英钠是否会影响二氢吡啶类钙拮抗剂尼索地平的药代动力学。
12名接受慢性苯妥英钠治疗的癫痫患者和12名年龄及性别匹配的健康对照受试者分别单次口服尼索地平（剂量分别为40毫克和20毫克）。采集血样长达48小时，通过毛细管气相色谱法测定血浆尼索地平水平。
患者的血浆尼索地平平均浓度低得多。以20毫克剂量标准化后的浓度-时间曲线下面积（AUC0-tn）的几何均值，患者为1.6微克/升/小时（95%置信区间，0.6 - 3.8微克/升/小时），而对照受试者为15.2（10.7 - 21.6）微克/升/小时（p < 0.002）。
这些结果表明苯妥英钠在临床上显著增加了尼索地平的首过代谢。鉴于相互作用的程度和变异性，禁止在接受慢性苯妥英钠治疗的患者中使用尼索地平。
