Dept. of Pharmacy, Marshfield Clinic, Marshfield, WI, United States.
Nemours Children's Health Systems-Jacksonville & Department of Neurology, Mayo Clinic - College of Medicine, 807 Children's Way, Jacksonville, FL, 32207, United States.
Seizure. 2018 Apr;57:76-79. doi: 10.1016/j.seizure.2018.03.003. Epub 2018 Mar 7.
Conversion to lamotrigine (LTG) monotherapy from sodium valproate (VPA) is complicated by the robust pharmacokinetic interaction between the two AEDs. This study examined changes in LTG serum concentrations immediately following VPA discontinuation.
Ten healthy female and male adult subjects were initiated on LTG (Lamictal) 10 mg orally every morning for 30 days and VPA (Depakote ER) 500 mg orally every morning for 14 days. Morning trough (pre-dose) venous blood samples were obtained for determination of LTG and VPA concentrations on study days 14, 15, 16, 18, 20, 22, 24, 26, 28, and 30. Following the collection of the blood sample on day 15, VPA was discontinued.
Despite stable LTG dosage serum concentrations on study day 20, 22, 24, 26, and 28, all were significantly lower compared to baseline (p < 0.05).
These observations demonstrate that the pharmacokinetic interaction between LTG and VPA is reversible, and that de-inhibition appears to follow a predictable time course. Complete offset, or reversal of this interaction takes place 10-14 days after VPA discontinuation. Our data also confirms the observation that LTG oral clearance may be inhibited by very low concentrations of VPA. These data support the conversion algorithm suggested by the manufacturer, and provide guidance to the clinician. These data provide clinically useful information in developing a dosing algorithm for converting patients to LTG monotherapy.
从丙戊酸钠（VPA）转换为拉莫三嗪（LTG）单药治疗很复杂，因为这两种 AED 之间存在强大的药代动力学相互作用。本研究检查了 VPA 停药后 LTG 血清浓度的变化。
10 名健康的成年男女受试者开始每天口服 LTG（拉莫三嗪）10mg，持续 30 天，每天口服 VPA（Depakote ER）500mg，持续 14 天。在研究第 14、15、16、18、20、22、24、26、28 和 30 天的早晨，采集静脉血样以测定 LTG 和 VPA 浓度。在第 15 天采集血样后，停止使用 VPA。
尽管在研究第 20、22、24、26 和 28 天 LTG 剂量稳定，但与基线相比，所有浓度均显著降低（p<0.05）。
这些观察结果表明，LTG 和 VPA 之间的药代动力学相互作用是可逆的，去抑制作用似乎遵循可预测的时间过程。VPA 停药后 10-14 天，完全消除或逆转这种相互作用。我们的数据还证实了 LTG 口服清除率可能被非常低浓度的 VPA 抑制的观察结果。这些数据支持制造商提出的转换算法，并为临床医生提供指导。这些数据为开发将患者转换为 LTG 单药治疗的剂量算法提供了临床有用的信息。
