Hussey E K, Dukes G E, Messenheimer J A, Brouwer K L, Donn K H, Krol T F, Hak L J
University of North Carolina, School of Pharmacy, Chapel Hill 27599.
Pharm Res. 1990 Nov;7(11):1172-6. doi: 10.1023/a:1015940527815.
The protein binding and pharmacokinetics of diazepam, ACC-9653 (a phenytoin prodrug), and phenytoin were evaluated in nine healthy male volunteers following administration of diazepam and ACC-9653, alone or concomitantly, in a randomized crossover design. No significant differences were observed in the fraction unbound or pharmacokinetic parameters of ACC-9653, phenytoin, or diazepam when ACC-9653 was administered alone compared to concomitant administration with diazepam. The phenytoin fraction unbound increased significantly with increased concentrations of ACC-9653, indicating displacement of phenytoin from its binding sites by ACC-9653. ACC-9653 also demonstrated concentration dependent binding. The lack of a significant pharmacokinetic drug interaction between ACC-9653 and diazepam suggests that these drugs may be safely administered together, although this conclusion should be confirmed in the intended patient population.
在一项随机交叉设计中，对9名健康男性志愿者给予地西泮和ACC - 9653（一种苯妥英前体药物），单独给药或联合给药，之后评估了地西泮、ACC - 9653和苯妥英的蛋白结合及药代动力学情况。与地西泮联合给药相比，单独给予ACC - 9653时，ACC - 9653、苯妥英或地西泮的游离分数或药代动力学参数未观察到显著差异。随着ACC - 9653浓度的增加，苯妥英的游离分数显著增加，表明ACC - 9653将苯妥英从其结合位点置换出来。ACC - 9653也表现出浓度依赖性结合。ACC - 9653与地西泮之间缺乏显著的药代动力学药物相互作用，提示这些药物可能可以安全地联合使用，尽管这一结论应在目标患者群体中得到证实。
