Calvo R, Aguilera L, Aguirre C, Rodríguez Sasiaín J M
Department of Pharmacology, University of Basque Country, Leioa, Vizcaya, Spain.
Int J Clin Pharmacol Res. 1989;9(1):59-63.
Non-esterified fatty acids have been shown to displace diazepam from its plasma binding sites both in vitro and in vivo. However, the binding of other benzodiazepines such as lorazepam is not affected in similar situations. Flunitrazepam exhibits a substantial degree of binding to plasma proteins, therefore it was deemed interesting to investigate the role of free fatty acids on flunitrazepam binding to human plasma proteins. Incubation of plasma with sodium oleate (1.5 and 3.0 microEq per ml) produced a decrease in the binding of flunitrazepam. The free fraction increased from 4.20 +/- 0.34 to 6.30 +/- 0.53 and to 22.18 +/- 1.28% respectively). Sodium heparin administration (10IU/kg, intravenously) increased free fatty acids levels and produced similar changes in the binding of flunitrazepam. After ten minutes of heparin administration free fatty acids increased from 0.16 +/- 0.03 mEq/l to 0.34 +/- 0.01 mEq/l and the free fraction of flunitrazepam in plasma increased from 3.70 +/- 0.22% to 6.20 +/- 1.24%. These binding data further support a relationship between increases in the concentrations of free fatty acids and decreases in the fraction of flunitrazepam bound to plasma proteins.
已证实在体外和体内，非酯化脂肪酸均可将地西泮从其血浆结合位点上置换下来。然而，在类似情况下，其他苯二氮䓬类药物如劳拉西泮的结合不受影响。氟硝西泮与血浆蛋白有较高程度的结合，因此，研究游离脂肪酸对氟硝西泮与人血浆蛋白结合的作用显得很有意思。用油酸（每毫升1.5和3.0微当量）孵育血浆会导致氟硝西泮结合减少。游离分数分别从4.20±0.34增加到6.30±0.53以及22.18±1.28%。静脉注射肝素钠（10IU/kg）会提高游离脂肪酸水平，并使氟硝西泮的结合产生类似变化。注射肝素十分钟后，游离脂肪酸从0.16±0.03毫当量/升增加到0.34±0.01毫当量/升，血浆中氟硝西泮的游离分数从3.70±0.22%增加到6.20±1.24%。这些结合数据进一步支持了游离脂肪酸浓度升高与氟硝西泮与血浆蛋白结合分数降低之间的关系。
