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.
conclusion:
It was the first time to investigate the initial dosage optimization of VPA in patients with bipolar disorder based on gender difference and combined used clozapine, providing reference for the precision drug use of VPA in clinical patients with bipolar disorder.
