Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication:: Results of a retrospective study
Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication:: Results of a retrospective study
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DOI：
10.1097/00007691-199904000-00007
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发表时间：
1999-04-01
影响因子：
2.5
通讯作者：
Jürgens, U
中科院分区：
文献类型：
--
作者：
May, TW;Rambeck, B;Jürgens, U
本回顾性研究的目的是探讨奥卡西平（OCBZ）和甲琥胺（MSM）对拉莫三嗪（LTG）血药浓度的影响。在合并和未合并丙戊酸（VPA）的患者中，检查了OCBZ与卡马西平（CBZ）相比的作用以及MSM对LTG血清浓度的影响。在常规药物监测中，共分析了222例患者的376份样本。仅当合并用药发生变化时，才考虑来自同一患者的两份或更多份血清样本。对于统计学评价，进行了回归分析方法和方差分析。对于方差分析，计算LTG血清浓度与LTG剂量/体重-水平-剂量比（LDR）的关系，单位为（μ g/mL）/（mg/kg），并比较不同药物组合。非线性回归分析显示，LTG剂量/体重、年龄、性别、合并用药种类对LTG血药浓度有显著影响（r（2）= 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LTG浓度比男性低约18%，年龄具有显著影响。这些数据表明，儿童的LTG浓度显著低于成人，按体重计算的LTG剂量相当，儿童可能更容易受到联合用药的酶诱导。甲琥胺对LTG代谢具有强烈的诱导作用，并显著降低LTG浓度（与LTG单药治疗相比约70%）。卡马西平也显著降低LTG浓度（54%）。OCBZ（29%）的诱导作用不太明显，但也很显著。MSM、CBZ和OCBZ与VPA联合给药时也观察到诱导作用：VPA单独给药可使LTG浓度增加约211%，而与MSM（8%）、CBZ（21%）或OCBZ（111%）联合给药时，LTG的增加显著较小。方差分析证实了回归分析的结果。在LTG治疗的患者中，如果添加或停用MSM，应考虑MSM对LTG浓度的影响。奥卡西平对LTG代谢的诱导作用不如CBZ明显。如果CBZ被OCBZ替代作为联合用药，则应预期LTG血清浓度增加。
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 (mu g/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 (r(2) = 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.