Effects of Sex Differences and Combined Use of Clozapine on Initial Dosage Optimization of Valproic Acid in Patients with Bipolar Disorder


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Аннотация

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.

Conclusion: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.

Об авторах

Wei Shen

Department of Pharmacy, The Suqian Clinical College of Xuzhou Medical University

Email: info@benthamscience.net

Ke Hu

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University

Email: info@benthamscience.net

Hao-Zhe Shi

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University

Email: info@benthamscience.net

Lei Jiang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University

Email: info@benthamscience.net

Yi-Jia Zhang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University

Email: info@benthamscience.net

Su-Mei He

Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Cun Zhang

Department of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Xiao Chen

School of Nursing, Xuzhou Medical University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Dong-Dong Wang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University

Автор, ответственный за переписку.
Email: info@benthamscience.net

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