Grimaldi R, Lecchini S, Crema F, Perucca E
Eur J Drug Metab Pharmacokinet. 1984 Oct-Dec;9(4):359-63. doi: 10.1007/BF03189686.
The effect of naproxen on the kinetics of free and total plasma valproic acid (VPA) was investigated in 6 normal volunteers by using a recently developed simple ultrafiltration technique associated with an immuno-enzymatic assay (Free Level System I, Syva). Each subject received a single oral dose of sodium valproate on two occasions: a) on a control day and b) during concurrent treatment with naproxen (500 mg b.i.d. for 5 consecutive days). Naproxen caused a slight but significant decrease in total plasma VPA levels but left free VPA levels essentially unchanged. The free VPA fraction increased with increasing total VPA concentrations: at equivalent values of total VPA, however, the free fraction was higher in the presence of naproxen. It is concluded that naproxen exerts a moderate displacing effect on protein bound VPA, thereby increasing the clearance of total drug but leaving essentially unchanged the clearance of free drug.
通过使用一种最近开发的与免疫酶测定法（自由水平系统I，Syva）相关的简单超滤技术，在6名正常志愿者中研究了萘普生对游离和总血浆丙戊酸（VPA）动力学的影响。每位受试者在两个不同时间接受单次口服丙戊酸钠剂量：a）在对照日；b）在同时服用萘普生期间（500mg，每日两次，连续5天）。萘普生导致总血浆VPA水平轻微但显著下降，但游离VPA水平基本保持不变。游离VPA分数随总VPA浓度增加而增加：然而，在总VPA等效值时，萘普生存在时游离分数更高。得出的结论是，萘普生对与蛋白结合的VPA有适度的置换作用，从而增加了总药物的清除率，但游离药物的清除率基本保持不变。
