Taylor J W, Alexander B, Lyon L W
Am J Hosp Pharm. 1981 Jan;38(1):93-5.
A case of phenytoin-disulfiram drug interaction is analyzed with a mathematical technique used in enzyme kinetics. Serum anticonvulsant levels, obtained before, during, and after disulfiram administration, were collected from hospital records retrospectively. Phenytoin kinetic constants--maximal velocity of metabolism (Vmax) and Michaelis-Menten constant (km)--before, during, and after disulfiram administration, were compared. The slopes (km) of the regression lines analyzed by a small sample t test for parallelism were not significantly different (p greater than 0.05). Y-intercept (Vmax) values obtained before (433 mg/day) and after (463 mg/day) disulfiram are both significantly different when compared with the y-intercept during (264 mg/day) disulfiram administration, by a small-sample t test for common intercept (p less than 0.05). Changes in the elimination rate of phenytoin or changes in y-intercept result from noncompetitive drug effects. It is concluded that disulfiram affects phenytoin's elimination rate by noncompetitive mechanisms.
运用酶动力学中的数学技术分析了一例苯妥英-双硫仑药物相互作用的病例。回顾性地从医院记录中收集了双硫仑给药前、给药期间和给药后的血清抗惊厥水平。比较了双硫仑给药前、给药期间和给药后的苯妥英动力学常数——最大代谢速度（Vmax）和米氏常数（km）。通过小样本t检验进行平行性分析得到的回归线斜率（km）无显著差异（p＞0.05）。通过小样本t检验进行共同截距分析可知，双硫仑给药前（433毫克/天）和给药后（463毫克/天）得到的Y截距（Vmax）值与给药期间（264毫克/天）的Y截距相比均有显著差异（p＜0.05）。苯妥英消除率的变化或Y截距的变化是由非竞争性药物效应引起的。得出的结论是，双硫仑通过非竞争性机制影响苯妥英的消除率。
