Tsanaclis L M, Allen J, Perucca E, Routledge P A, Richens A
Br J Clin Pharmacol. 1984 Jul;18(1):17-20. doi: 10.1111/j.1365-2125.1984.tb05015.x.
The plasma protein binding of phenytoin was studied in nine epileptic patients before and during addition of sodium valproate to the drug therapy. The free phenytoin fraction in plasma was significantly greater during sodium valproate treatment. The mean free fraction rose from 0.135 +/- 0.019 (s.d.) to 0.182 +/- 0.030. Total plasma phenytoin concentration fell significantly from a range of 4.3-26.2 micrograms/ml to 3.4-19.8 micrograms/ml during sodium valproate treatment. Neither the free plasma concentration nor the saliva concentration of phenytoin was significantly altered by sodium valproate. No significant correlation was found between plasma valproic acid concentrations and the change in phenytoin binding. We conclude that valproic acid displaces phenytoin from plasma protein binding sites but does not inhibit its metabolism.
在9名癫痫患者中，于药物治疗中添加丙戊酸钠之前及期间，对苯妥英的血浆蛋白结合情况进行了研究。在丙戊酸钠治疗期间，血浆中游离苯妥英部分显著增加。游离部分的平均值从0.135±0.019（标准差）升至0.182±0.030。在丙戊酸钠治疗期间，血浆苯妥英总浓度从4.3 - 26.2微克/毫升的范围显著降至3.4 - 19.8微克/毫升。丙戊酸钠对苯妥英的游离血浆浓度及唾液浓度均无显著影响。未发现血浆丙戊酸浓度与苯妥英结合变化之间存在显著相关性。我们得出结论，丙戊酸可将苯妥英从血浆蛋白结合位点上置换下来，但并不抑制其代谢。
