May T W, Rambeck B, Jürgens U
Department of Biochemistry, Gesellschaft für Epilepsieforschung, Bielefeld, Germany.
Ther Drug Monit. 1999 Apr;21(2):175-81. doi: 10.1097/00007691-199904000-00007.
The aim of this retrospective study was to investigate the influence of oxcarbazepine (OCBZ) and methsuximide (MSM) on lamotrigine (LTG) serum concentrations. The effect of OCBZ compared to carbamazepine (CBZ) and the effect of MSM on LTG serum concentrations were examined in patients with and without valproic acid (VPA) comedication. Altogether, 376 samples from 222 patients were analyzed in routine drug monitoring. Two or more serum samples from the same patient were considered only if the comedication had been changed. For statistical evaluation, regression analytical methods and an analysis of variance were performed. For the analysis of variance, the LTG serum concentration in relation to LTG dose/ body weight--level-to-dose ratio (LDR), in (microg/mL)/(mg/kg)--was calculated and compared for different drug combinations. The nonlinear regression analysis including the LTG dose per body weight, age, gender, and the different kinds of comedication revealed that these variables have a significant influence on LTG serum concentration (r2 = 0.724). The relationship between LTG dose/body weight and serum concentration deviates only slightly from linearity, the LTG concentration was about 18% lower in women than in men, and age had a significant influence. The data indicate that children have significantly lower LTG concentrations than adults on a comparable LTG dose per body weight and that children may be more prone to enzyme induction by comedicated drugs. Methsuximide has a strong inducing effect on the LTG metabolism and decreases the LTG concentrations markedly (about 70% compared to LTG monotherapy). Carbamazepine also reduces the LTG concentrations considerably (by 54%). The inducing effect of OCBZ (29%) was less pronounced but also significant. The inducing effect of MSM, CBZ, and OCBZ was also seen in combination with VPA: VPA alone increases the LTG concentration approximately 211%, whereas in addition to MSM (8%), CBZ (21%), or OCBZ (111%), the increase of LTG was significantly smaller. The analysis of variance confirmed the results of the regression analysis. The effect of MSM on the LTG concentration should be considered if MSM is added or withdrawn in patients treated with LTG. Oxcarbazepine had a less pronounced inducing effect on LTG metabolism compared to CBZ. If CBZ is replaced by OCBZ as comedication, an increase in LTG serum concentrations should be expected.
这项回顾性研究的目的是调查奥卡西平（OCBZ）和甲琥胺（MSM）对拉莫三嗪（LTG）血清浓度的影响。在有和没有丙戊酸（VPA）合并用药的患者中，研究了OCBZ与卡马西平（CBZ）相比的效果以及MSM对LTG血清浓度的影响。在常规药物监测中，共分析了来自222例患者的376份样本。仅当合并用药发生变化时，才考虑同一患者的两份或更多份血清样本。为进行统计评估，采用了回归分析方法和方差分析。对于方差分析，计算了与LTG剂量/体重相关的LTG血清浓度——水平与剂量比（LDR），单位为（μg/mL）/（mg/kg），并比较了不同药物组合的情况。包括LTG每体重剂量、年龄、性别以及不同类型合并用药的非线性回归分析表明，这些变量对LTG血清浓度有显著影响（r2 = 0.724）。LTG剂量/体重与血清浓度之间的关系仅略微偏离线性，女性的LTG浓度比男性低约18%，且年龄有显著影响。数据表明，在每体重剂量相当的情况下，儿童的LTG浓度显著低于成人，且儿童可能更容易受到合并用药的酶诱导作用影响。甲琥胺对LTG代谢有强烈的诱导作用，显著降低LTG浓度（与LTG单药治疗相比约降低70%）。卡马西平也会大幅降低LTG浓度（降低54%）。奥卡西平的诱导作用（29%）虽不那么明显，但也具有显著性。MSM、CBZ和OCBZ与VPA联合使用时也有诱导作用：单独使用VPA可使LTG浓度增加约211%，而在联合使用MSM（8%）、CBZ（21%）或OCBZ（111%）时，LTG的增加显著较小。方差分析证实了回归分析的结果。在接受LTG治疗的患者中，如果添加或停用MSM，应考虑其对LTG浓度的影响。与CBZ相比，奥卡西平对LTG代谢的诱导作用不那么明显。如果将CBZ替换为OCBZ作为合并用药，预计LTG血清浓度会升高。
