Randinitis E J, Buchanan R A, Kinkel A W
Pharmacokinetic/Drug Metabolism Department, Parke-Davis Pharmaceutical Research Division, Warner Lambert Co., Ann Arbor, MI 48105.
Epilepsia. 1990 Jul-Aug;31(4):458-64. doi: 10.1111/j.1528-1157.1990.tb05503.x.
The pharmacokinetic profile of a newly developed Dilantin 300-mg Kapseal formulation was compared with that of currently marketed Dilantin 100-mg Kapseals in both a 300-mg single-dose bioequivalence study in nine healthy volunteers and a once-daily 300-mg multiple-dose study in 18 patients with seizures. Results of these studies indicate the rate and extent of absorption of the 300-mg extended phenytoin (PHT) sodium capsule formulation are similar to that of 100-mg extended PHT sodium capsules based on PHT plasma maximum concentrations and time to achieve them (Cmax, tmax), and area under the curve (AUC) values and the urinary excretion of total hydroxy phenylhydantoin (HPPH) in the single-dose study and steady-state PHT plasma Cmax, tmax, minimum plasma concentrations (Cmin), and AUC values and urinary excretion of total HPPH in the multiple-dose study. Control of seizures in patients was equally maintained on a once-daily 300-mg multiple-dosing regimen administered as either one 300-mg extended PHT sodium capsule daily or three 100-mg extended PHT sodium capsules daily. Therefore, 300-mg extended PHT sodium capsules can be safely and effectively interchanged with three 100-mg extended PHT sodium capsules in patients requiring a once-daily 300-mg PHT sodium dosing regimen.
在一项针对9名健康志愿者的300毫克单剂量生物等效性研究以及一项针对18名癫痫患者的每日一次300毫克多剂量研究中，将新开发的300毫克苯妥英钠胶囊制剂的药代动力学特征与目前市场上销售的100毫克苯妥英钠胶囊进行了比较。这些研究结果表明，基于苯妥英钠血浆最大浓度及其达到时间（Cmax、tmax）、曲线下面积（AUC）值以及单剂量研究中总羟基苯妥英（HPPH）的尿排泄量，以及多剂量研究中稳态苯妥英钠血浆Cmax、tmax、最低血浆浓度（Cmin）、AUC值和总HPPH的尿排泄量，300毫克缓释苯妥英钠胶囊制剂的吸收速率和程度与100毫克缓释苯妥英钠胶囊相似。在每日一次300毫克多剂量给药方案中，无论是每日服用一粒300毫克缓释苯妥英钠胶囊还是每日服用三粒100毫克缓释苯妥英钠胶囊，患者的癫痫控制情况均保持相同。因此，在需要每日一次300毫克苯妥英钠给药方案的患者中，300毫克缓释苯妥英钠胶囊可安全有效地与三粒100毫克缓释苯妥英钠胶囊互换使用。
