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. 2022 Mar;78(3):405-418.
doi: 10.1007/s00228-021-03246-2. Epub 2021 Dec 2.

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder

Yan-Nan Zang  1   2 , Wei Guo  1   2 , Meng-Xi Niu  1   2 , Shuang Bao  1   2 , Qian Wang  1   2 , Yan Wang  1   2 , Fang Dong  1   2 , An-Ning Li  1   2 , Can-Jun Ruan  3   4
Affiliations

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder

Yan-Nan Zang et al. Eur J Clin Pharmacol. 2022 Mar.

Abstract

Purpose: To develop and validate a population pharmacokinetic (PPK) model of valproic acid (VPA) in adult Chinese patients with bipolar disorder, and provide guidance for individualized therapy in this population.

Methods: A total of 1104 serum concentrations from 272 patients were collected in this study. The data analysis was performed using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, biological characteristics, and concomitant medications. Bootstrap validation (1000 runs), normalized prediction distribution error (NPDE), and external validation of 50 patients were employed to evaluate the final model.

Results: A one-compartment model with first-order absorption and elimination was developed for VPA extended-release tablets. VPA clearance was significantly influenced by three variables: sex (12% higher in male patients), daily dose (increasing with the 0.13 exponent), and body weight (increasing with the 0.56 exponent). Typical values for the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) for a female patient weighing 70 kg administered VPA 1000 mg/day were 0.18 h-1, 0.46 L/h, and 12.84 L, respectively. The results of model evaluation indicated a good stable and precise performance of the final model.

Conclusions: A qualified PPK model of VPA was developed in Chinese patients with bipolar disorder. This model could be used as a suitable tool for the personalization of VPA dosing for bipolar patients.

Keywords: Bipolar disorder; Population pharmacokinetics; Valproic acid.

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References

    1. McIntyre RS, Berk M, Brietzke E, Goldstein BI, Lopez-Jaramillo C, Kessing LV, Malhi GS, Nierenberg AA, Rosenblat JD, Majeed A, Vieta E, Vinberg M, Young AH, Mansur RB (2020) Bipolar disorders. Lancet 396(10265):1841–1856. https://doi.org/10.1016/S0140-6736(20)31544-0 - DOI - PubMed
    1. Rantala MJ, Luoto S, Borraz-Leon JI, Krams I (2021) Bipolar disorder: An evolutionary psychoneuroimmunological approach. Neurosci Biobehav Rev 122:28–37. https://doi.org/10.1016/j.neubiorev.2020.12.031 - DOI - PubMed
    1. Vigo D, Thornicroft G, Atun R (2016) Estimating the true global burden of mental illness. Lancet Psychiatry 3(2):171–178. https://doi.org/10.1016/S2215-0366(15)00505-2 - DOI - PubMed
    1. Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z (2011) Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 68(3):241–251. https://doi.org/10.1001/archgenpsychiatry.2011.12 - DOI - PubMed - PMC
    1. Bowden CL (2003) Valproate. Bipolar Disord 5(3):189–202. https://doi.org/10.1034/j.1399-5618.2003.00031.x - DOI - PubMed

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