Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Japan.
Biol Pharm Bull. 2012;35(6):971-4. doi: 10.1248/bpb.35.971.
Therapeutic drug monitoring of valproic acid (VPA) is essential to prevent toxicity, but the correlation between plasma ammonia level and serum VPA concentration remains unclear. We examined the correlation of plasma ammonia level with VPA dose and serum trough concentrations of total and free VPA in Japanese patients with epilepsy. Thirty-eight data sets from 19 Japanese patients with epilepsy were analyzed. The relations of VPA dose and serum total and free VPA concentrations with plasma ammonia level, and the breakpoints of VPA parameters predicting hyperammonemia (plasma ammonia higher than 60 µmol/L) were analyzed. A significant positive correlation was observed between plasma ammonia level and VPA dose (r(s)=0.56, p=0.00062), serum trough total VPA concentration (r(s)=0.55, p=0.00086) and serum trough free VPA concentration (r(s)=0.58, p=0.00041). The breakpoints predicting hyperammonemia were VPA dose of 30.4 mg/kg, serum trough total VPA concentration of 90.9 µg/mL, and serum trough free VPA concentration of 8.65 µg/mL, with impurity reductions at 1.35, 1.35 and 2.02, respectively. These findings suggest that serum trough concentration of free VPA is the most reliable predictor for hyperammonemia, and that the risk of developing hyperammonemia may increase in patients with serum trough free VPA concentrations higher than 8.65 µg/mL.
我们检测了癫痫患者的血浆氨水平与丙戊酸（VPA）剂量和血清总游离 VPA 浓度的相关性。分析了 19 例日本癫痫患者的 38 组数据。分析了 VPA 剂量和血清总游离 VPA 浓度与血浆氨水平的关系，以及预测高氨血症（血浆氨高于 60 μmol/L）的 VPA 参数的临界点。血浆氨水平与 VPA 剂量（r(s)=0.56，p=0.00062）、血清谷值总 VPA 浓度（r(s)=0.55，p=0.00086）和血清谷值游离 VPA 浓度（r(s)=0.58，p=0.00041）呈显著正相关。预测高氨血症的临界点为 VPA 剂量 30.4mg/kg，血清谷值总 VPA 浓度 90.9μg/mL，血清谷值游离 VPA 浓度 8.65μg/mL，杂质减少分别为 1.35、1.35 和 2.02。这些发现表明，游离 VPA 的血清谷浓度是预测高氨血症最可靠的指标，血清游离 VPA 浓度高于 8.65μg/mL 的患者发生高氨血症的风险可能会增加。
