Abstract：
BACKGROUND: Due to the narrow therapeutic window and large pharmacokinetic variation of valproic acid (VPA), it is difficult to make an optimal dosage regimen. The present study aims to optimize the initial dosage of VPA in patients with bipolar disorder.
METHODS: A total of 126 patients with bipolar disorder treated by VPA were included to construct the VPA population pharmacokinetic model retrospectively. Sex differences and combined use of clozapine were found to significantly affect VPA clearance in patients with bipolar disorder. The initial dosage of VPA was further optimized in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively.
RESULTS: The CL/F and V/F of VPA in patients with bipolar disorder were 11.3 L/h and 36.4 L, respectively. It was found that sex differences and combined use of clozapine significantly affected VPA clearance in patients with bipolar disorder. At the same weight, the VPA clearance rates were 1.134, 1, 1.276884, and 1.126 in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. This study further optimized the initial dosage of VPA in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively.
CONCLUSIONS: This study is the first to investigate the initial dosage optimization of VPA in patients with bipolar disorder based on sex differences and the combined use of clozapine. Male patients had higher clearance, and the recommended initial dose decreased with increasing weight, providing a reference for the precision drug use of VPA in clinical patients with bipolar disorder.
METHODS: A total of 126 patients with bipolar disorder treated by VPA were included to construct the VPA population pharmacokinetic model retrospectively. Sex differences and combined use of clozapine were found to significantly affect VPA clearance in patients with bipolar disorder. The initial dosage of VPA was further optimized in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively.
RESULTS: The CL/F and V/F of VPA in patients with bipolar disorder were 11.3 L/h and 36.4 L, respectively. It was found that sex differences and combined use of clozapine significantly affected VPA clearance in patients with bipolar disorder. At the same weight, the VPA clearance rates were 1.134, 1, 1.276884, and 1.126 in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. This study further optimized the initial dosage of VPA in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively.
CONCLUSIONS: This study is the first to investigate the initial dosage optimization of VPA in patients with bipolar disorder based on sex differences and the combined use of clozapine. Male patients had higher clearance, and the recommended initial dose decreased with increasing weight, providing a reference for the precision drug use of VPA in clinical patients with bipolar disorder.
摘要：
背景：由于丙戊酸（VPA）的治疗窗窄和药代动力学变化大，很难制定最佳剂量方案。本研究旨在优化双相情感障碍患者VPA的初始剂量。
方法：纳入126例接受VPA治疗的双相情感障碍患者，回顾性构建VPA群体药代动力学模型。发现性别差异和氯氮平的联合使用显着影响双相情感障碍患者的VPA清除率。在没有联合使用氯氮平的男性患者中，VPA的初始剂量进一步优化，没有联合使用氯氮平的女性患者，男性患者联合使用氯氮平，和女性患者联合使用氯氮平，分别。
结果：双相情感障碍患者VPA的CL/F和V/F分别为11.3L/h和36.4L,分别。发现性别差异和氯氮平的联合使用显着影响双相情感障碍患者的VPA清除率。同样的重量,未联合使用氯氮平的男性患者的VPA清除率分别为1.134、1、1.276884和1.126，没有联合使用氯氮平的女性患者，男性患者联合使用氯氮平，和女性患者联合使用氯氮平，分别。本研究进一步优化了未联合使用氯氮平的男性患者VPA的初始剂量，没有联合使用氯氮平的女性患者，男性患者联合使用氯氮平，和女性患者联合使用氯氮平，分别。
结论：本研究首次基于性别差异和联合使用氯氮平对双相情感障碍患者进行VPA初始剂量优化。男性患者的清除率较高，推荐的初始剂量随着体重的增加而减少，为临床双相情感障碍患者VPA精准用药提供参考。
方法：纳入126例接受VPA治疗的双相情感障碍患者，回顾性构建VPA群体药代动力学模型。发现性别差异和氯氮平的联合使用显着影响双相情感障碍患者的VPA清除率。在没有联合使用氯氮平的男性患者中，VPA的初始剂量进一步优化，没有联合使用氯氮平的女性患者，男性患者联合使用氯氮平，和女性患者联合使用氯氮平，分别。
结果：双相情感障碍患者VPA的CL/F和V/F分别为11.3L/h和36.4L,分别。发现性别差异和氯氮平的联合使用显着影响双相情感障碍患者的VPA清除率。同样的重量,未联合使用氯氮平的男性患者的VPA清除率分别为1.134、1、1.276884和1.126，没有联合使用氯氮平的女性患者，男性患者联合使用氯氮平，和女性患者联合使用氯氮平，分别。本研究进一步优化了未联合使用氯氮平的男性患者VPA的初始剂量，没有联合使用氯氮平的女性患者，男性患者联合使用氯氮平，和女性患者联合使用氯氮平，分别。
结论：本研究首次基于性别差异和联合使用氯氮平对双相情感障碍患者进行VPA初始剂量优化。男性患者的清除率较高，推荐的初始剂量随着体重的增加而减少，为临床双相情感障碍患者VPA精准用药提供参考。
