Ieiri I, Morioka T, Ichimiya T, Nishio S, Fukui M, Ohtsubo K, Higuchi S
Division of Pharmaceutical Science, Kyushu University, Fukuoka, Japan.
Ther Drug Monit. 1995 Feb;17(1):6-11. doi: 10.1097/00007691-199502000-00002.
Pharmacokinetics of valproic acid sustained-release preparation (VPA-SR) were studied in nine patients undergoing surgery for brain tumor. Total (t) and free (f) serum concentrations were analyzed in samples drawn during the day of brain surgery and compared with levels from a postoperative day. The area under the curve (AUCt) and clearance (CLt) of the total concentration did not differ on these occasions. In contrast, statistically significant differences were observed in AUCf and CLf between the two occasions; increased AUCf and decreased CLf were observed on the day of surgery. A significant relation was found between the average free fraction (AUCf/AUCt on operation day per AUCf/AUCt on postoperative day) and estimated blood loss during operation (r = 0.82; p < 0.001). In addition, a significant relation was found between simple free fraction and the intraoperative albumin level in serum (r = -0.68; p < 0.001). These findings indicate that the increased VPA free concentration is due to low serum albumin level secondary to blood loss and that there has been a decrease in intrinsic clearance during operation.
对9例接受脑肿瘤手术的患者研究了丙戊酸缓释制剂（VPA-SR）的药代动力学。在脑手术当天采集的样本中分析了总血清浓度（t）和游离血清浓度（f），并与术后一天的浓度水平进行比较。在这些情况下，总浓度的曲线下面积（AUCt）和清除率（CLt）没有差异。相比之下，两次检测的AUCf和CLf存在统计学显著差异；手术当天观察到AUCf增加和CLf降低。发现平均游离分数（手术日的AUCf/AUCt与术后日的AUCf/AUCt之比）与手术期间估计失血量之间存在显著相关性（r = 0.82；p < 0.001）。此外，发现简单游离分数与血清术中白蛋白水平之间存在显著相关性（r = -0.68；p < 0.001）。这些发现表明，VPA游离浓度增加是由于失血继发的血清白蛋白水平降低，并且手术期间内在清除率有所下降。
