磷苯妥英钠注射液人体药代动力学研究

Pharmacokinetics of fosphenytoin sodium injection in Chinese healthy volunteers

目的:研究健康受试者单次静脉滴注不同剂量磷苯妥英钠注射液后磷苯妥英及其活性代谢物苯妥英的体内药动学特征。方法:24名健康受试者分别接受静脉滴注600mg和900mg剂量的磷苯妥英钠注射液,HPLC法测定血药浓度,使用DAS2.0软件计算药动学参数。结果:受试者静脉注射600、900mg剂量磷苯妥英钠注射液后磷苯妥英主要药动学参数Cmax分别为(89.3±14.9)、(110.5±17.2)mg/L;tmax分别为(0.46±0.08)、(0.46±0.08)h;AUC0-t分别为(56.5±11.3)、(71.2±13.8)mg·h·L-1;苯妥英主要药动学参数Cmax分别为(8.36±0.92)、(11.98±1.07)mg/L;tmax分别为(1.1±0.3)、(1.3±0.3)h;AUC0-t分别为(222.7±47.8)、(355.9±72.6)mg·h·L-1。结论:单次静脉滴注600~900mg剂量范围内的磷苯妥英钠注射液,其母药磷苯妥英及其活性代谢产物苯妥英的药动学特征均符合一级动力学。磷苯妥英钠注射液在中国人体内的药动学行为与外国文献报道基本一致。

AIM： To investigate the pharmacokinetics of fosphenytoin sodium injection at single dose in Chinese healthy volunteers. METHODS： The pharmacokinetics of intravenous infusing fosphenytoin sodium injection at different dose levels （600mg and 900mg） was studied in 24 healthy volunteers.The drug concentrations in plasma samples were assayed by HPLC, and the pharmacokinetic parameters were calculated by DAS2.0 software. RESULTS： Among 24 healthy subjects, the main pharmacokinetic parameters of fosphenytoin after single dose of 600 mg and 900 mg were as follows： Cmax were （89.3 ± 14.9）, （110.5 ± 17.2） mg/L-1; Tmax were （0.46 ± 0.08）, （0.46 ± 0.08） h; AUC0-t were （56.5 ± 11.3）, （71.2 ± 13.8） mg？h？L-1; for phenytoin, they were Cmax （8.36 ± 0.92）, （11.98 ± 1.07） mg？L-1; Tmax（1.1 ± 0.3）, （1.3 ± 0.3） h; AUC0-t（222.7 ± 47.8）, （355.9 ± 72.6） mg？h？L-1, respectively. CONCLUSION： After 600 mg^900 mg single dose infusion of fosphenytoin sodium injection, the pharmacokinetic results show that both fosphenytoin and phenytoin exhibit first order kinetic characteristics in such a dose. And the pharmacokinetic characteristics of fosphenytoin sodium injection are consistent with foreign reports.