Wilder B J, Campbell K, Ramsay R E, Garnett W R, Pellock J M, Henkin S A, Kugler A R
Department of Neurology, Veterans Affairs Medical Center, Gainesville, Fla, USA.
Arch Neurol. 1996 Aug;53(8):764-8. doi: 10.1001/archneur.1996.00550080082016.
Safety, tolerability, and pharmacokinetics of fosphenytoin sodium, a water-soluble phenytoin prodrug, were investigated after a temporary substitution of intramuscular fosphenytoin for oral phenytoin sodium in 240 epileptic or neurosurgical patients taking oral phenytoin sodium (100-500 mg/d).
Patients were randomly assigned to 1 of 2 parallel groups. During screening and follow-up, patients were maintained on a regimen of oral phenytoin at an individualized dose. During treatment, the phenytoin-treated patients received intramuscular placebo and their prescribed dose of oral phenytoin; the fosphenytoin-treated patients received oral placebo and intramuscular fosphenytoin equimolar to their phenytoin dose.
Both groups had similar types and frequencies of mild to moderate adverse events. Fosphenytoin was as well tolerated as intramuscular placebo at the injection site. Intramuscular fosphenytoin equimolar to a patient's oral phenytoin dose produced equal or greater plasma phenytoin concentrations.
Dosing adjustments are not required when intramuscular fosphenytoin is temporarily substituted or oral phenytoin therapy is resumed. Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible.
在240例服用口服苯妥英钠（100 - 500毫克/天）的癫痫或神经外科患者中，将肌肉注射磷苯妥英钠临时替代口服苯妥英钠后，对水溶性苯妥英前体药物磷苯妥英钠的安全性、耐受性和药代动力学进行了研究。
患者被随机分配到2个平行组中的1组。在筛查和随访期间，患者维持个体化剂量的口服苯妥英治疗方案。治疗期间，接受苯妥英治疗的患者接受肌肉注射安慰剂和其规定剂量的口服苯妥英；接受磷苯妥英治疗的患者接受口服安慰剂和与苯妥英剂量等摩尔的肌肉注射磷苯妥英。
两组轻度至中度不良事件的类型和频率相似。在注射部位，磷苯妥英的耐受性与肌肉注射安慰剂相同。与患者口服苯妥英剂量等摩尔的肌肉注射磷苯妥英产生的血浆苯妥英浓度相等或更高。
当临时替代肌肉注射磷苯妥英或恢复口服苯妥英治疗时，无需调整剂量。当口服给药不可行时，肌肉注射磷苯妥英是口服苯妥英的一种安全且耐受性良好的替代方法。
