Albani F, Riva R, Procaccianti G, Baruzzi A, Perucca E
Epilepsia. 1983 Feb;24(1):65-73. doi: 10.1111/j.1528-1157.1983.tb04867.x.
The effect of sample incubation and storage on the protein binding of the antiepileptic drug valproic acid (VPA) and on the concentration of free fatty acids (FFA) was investigated in serum and plasma collected from four normal volunteers. Both the free fraction of VPA and the concentration of FFA increased progressively with time when samples were incubated at 4 to 37 degrees C. These effects occurred to the same extent in both serum and heparinized plasma. At 4 degrees C and at room temperature, the increase in free drug fraction was relatively small (18 and 25% respectively at 24 h), whereas at 37 degrees C it was quite considerable (24% at 8 h and 40% at 24 h). At room temperature, FFA rose on average by 22% at 4 h, 34% at 8 h, and 86% at 24 h, whereas at 37 degrees C the increases at the same incubation times were 59, 90, and 160%, respectively. There was a strong positive relationship between changes in free VPA fraction and FFA content of the samples. The time-dependent changes in VPA binding capacity described in this study may lead to overestimation of the actual free concentration in vivo, especially when this is estimated by equilibrium dialysis or ultracentrifugation techniques requiring long incubation (centrifugation) times at 37 degrees C.
在从四名正常志愿者采集的血清和血浆中，研究了样品孵育和储存对抗癫痫药物丙戊酸（VPA）的蛋白质结合以及游离脂肪酸（FFA）浓度的影响。当样品在4至37摄氏度下孵育时，VPA的游离分数和FFA的浓度均随时间逐渐增加。血清和肝素化血浆中的这些影响程度相同。在4摄氏度和室温下，游离药物分数的增加相对较小（24小时时分别为18%和25%），而在37摄氏度时则相当可观（8小时时为24%，24小时时为40%）。在室温下，FFA在4小时时平均升高22%，8小时时升高34%，24小时时升高86%，而在37摄氏度下，相同孵育时间的升高分别为59%、90%和160%。样品中游离VPA分数的变化与FFA含量之间存在很强的正相关关系。本研究中描述的VPA结合能力的时间依赖性变化可能导致对体内实际游离浓度的高估，尤其是当通过平衡透析或超速离心技术进行估计时，这些技术需要在37摄氏度下长时间孵育（离心）。
