Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Ther Drug Monit. 2010 Feb;32(1):19-29. doi: 10.1097/FTD.0b013e3181c13a30.
To review the pharmacokinetic literature regarding valproic acid (VPA) in patients with bipolar affective disorder to evaluate the appropriateness of routine therapeutic drug monitoring (TDM) of VPA in this population. Embase, Medline, Biosis, Cumulated Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Systematic Reviews databases (to July 2009) were searched (terms: valproate, valproic acid, valproate semisodium, divalproex, bipolar disorder, mania, bipolar affective disorder, assay, concentration, drug level, serum level, plasma level, therapeutic drug monitoring, drug monitoring, pharmacokinetics). A 9-step decision-making algorithm was applied to the available VPA literature in the bipolar population. VPA has been established as effective first-line therapy in the treatment of bipolar mania. Commercial assays are available to accurately measure VPA levels with good sensitivity and precision. Wide interpatient variability in VPA pharmacokinetic parameters and long anticipated treatment durations favor the use of TDM in the bipolar patient. Conversely, correlations between VPA levels and pharmacologic response in humans, and specifically patients with bipolar affective disorder are unclear. Compared with other agents known to have narrow therapeutic ranges, VPA does not seem to share this characteristic. Furthermore, the clinical efficacy and toxicity of VPA may be assessed in ways other than TDM, allowing for contributions by health care professionals, patients, and family members. Despite the development of effective and widely available VPA assays, routine monitoring of VPA concentrations in the general bipolar affective population does not seem warranted. However, TDM may enhance usual clinical monitoring in situations involving unusual VPA metabolism, polytherapy with clinically relevant drug interactions, or as part of a comprehensive assessment of treatment compliance.
回顾有关双相情感障碍患者中丙戊酸（VPA）的药代动力学文献，以评估在该人群中常规治疗药物监测（TDM）VPA 的适当性。检索了 Embase、Medline、Biosis、护理与联合健康文献累积索引（CINAHL）和 Cochrane 系统评价数据库（截至 2009 年 7 月）（术语：丙戊酸盐、丙戊酸、丙戊酸钠半水合物、双丙戊酸钠、双相障碍、躁狂、双相情感障碍、测定、浓度、药物水平、血清水平、血浆水平、治疗药物监测、药物监测、药代动力学）。对双相人群中可用的 VPA 文献应用了 9 步决策算法。VPA 已被确立为治疗双相躁狂的有效一线治疗药物。现已有商业检测方法可准确测量 VPA 水平，具有良好的灵敏度和精密度。VPA 药代动力学参数的个体间差异很大，预期治疗时间长，这有利于在双相患者中进行 TDM。相反，VPA 水平与人类药理反应之间的相关性，特别是与双相情感障碍患者之间的相关性尚不清楚。与其他具有狭窄治疗范围的已知药物相比，VPA 似乎不具有这种特征。此外，VPA 的临床疗效和毒性可以通过 TDM 以外的其他方式进行评估，这允许医疗保健专业人员、患者和家庭成员做出贡献。尽管开发了有效的、广泛可用的 VPA 检测方法，但在一般的双相情感障碍人群中，似乎没有必要常规监测 VPA 浓度。但是，在涉及不寻常的 VPA 代谢、与临床相关的药物相互作用的多药治疗或作为全面评估治疗依从性的一部分的情况下，TDM 可能会增强常规临床监测。
