Lardizabal David V, Morris Harold H, Hovinga Collin A, Del Mar Carreño Maria
Department of Neurology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Epilepsia. 2003 Apr;44(4):536-9. doi: 10.1046/j.1528-1157.2003.46902.x.
To investigate the tolerability and pharmacokinetics of oral loading with lamotrigine (LTG) among epilepsy patients after temporary drug discontinuation in an epilepsy monitoring unit.
We conducted a pilot study among epilepsy patients (18 years or older) receiving maintenance doses of LTG. LTG was discontinued on admission and restarted at the end of epilepsy monitoring. LTG was given as a single oral dose calculated based on the population expected volume of distribution (Vd, 1.0 L/kg) and target blood level on admission. Baseline and serial blood levels of LTG were determined hourly for 10 to 12 h after the loading dose.
(a) frequency of patients with side effects; (b) time to maximum concentration (Tmax), maximum concentration (Cmax), actual volume of distribution, and half-life.
Twenty-four patients received a single oral load of LTG (mean, 6.5 +/- 2.7 mg/kg). Overall, LTG loading was well tolerated with no serious adverse events or skin rash observed. Two patients had transient and mild nausea 1 to 2 h after the oral load. The mean estimated pharmacokinetic parameters are as follows: Tmax, 3.1 +/- 2.1 h; Cmax, 8.2 +/- 6.5 mg/L; Vd, 1.1 +/- 1.0 L/kg; clearance, 0.08 +/- 0.08 mg/L/h; half-life, 22 +/- 30 h. All patients reached their target blood levels.
Epilepsy patients temporarily discontinued from LTG can be restarted with a single oral loading dose. This was well tolerated, and therapeutic levels can be achieved within 1 to 3 h.
在癫痫监测单元中，研究癫痫患者临时停药后口服负荷剂量拉莫三嗪（LTG）的耐受性和药代动力学。
我们对接受LTG维持剂量治疗的癫痫患者（18岁及以上）进行了一项试点研究。患者入院时停用LTG，在癫痫监测结束时重新开始用药。根据人群预期分布容积（Vd，1.0 L/kg）和入院时的目标血药浓度计算，给予患者单次口服LTG负荷剂量。负荷剂量给药后10至12小时内，每小时测定LTG的基线血药浓度和系列血药浓度。
（a）出现副作用的患者频率；（b）达峰时间（Tmax）、最大浓度（Cmax）、实际分布容积和半衰期。
24例患者接受了单次口服LTG负荷剂量（平均剂量为6.5±2.7 mg/kg）。总体而言，LTG负荷剂量耐受性良好，未观察到严重不良事件或皮疹。两名患者在口服负荷剂量后1至2小时出现短暂轻度恶心。平均估计药代动力学参数如下：Tmax为3.1±2.1小时；Cmax为8.2±6.5 mg/L；Vd为1.1±1.0 L/kg；清除率为0.08±0.08 mg/L/h；半衰期为22±30小时。所有患者均达到目标血药浓度。
临时停用LTG的癫痫患者可单次口服负荷剂量重新开始用药。该方法耐受性良好，可在1至3小时内达到治疗血药浓度。
