Noskova T Yu, Abaimov D A, Sariev A K, Fedin P A, Krasnikov A V, Shvedkov V V, Sejfulla R D
Research Center of Neurology, Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(1):23-29. doi: 10.17116/jnevro20181181123-29.
To estimate pharmacokinetic variability of lamotrigine (LTG) and its clinical significance.
One hundred patients, including 74 women, aged from 18 to 77 years (38.23±14.37 years), with focal epilepsy were examined. Monotherapy with LTG was administered to 54 patients, duotherapy to 46 patients (LTG and valproic acid combination to 27 patients, LTG and liver enzymes inducers to 19 patients). Patients underwent procedures of therapeutic drug monitoring (TDM). Minimal (Css) and maximal (Css) steady-state LTG plasma concentrations, and concentration-to-weight ratio (CDR) were calculated.
In patients who used LTG in monotherapy, LTG Css was 5.6±4.65 mg/l, Css 7.59±5.54 mg/l. In the group that received LTG in combination with valproate, LTG Сss was 7.8 [5.4; 11.8] mg / l and Css 11.4 [7.3; 15.3] mg/l. In the group that received LTG in combination with drug-inducers of glucuronidation, Css was 2.5 [1.99; 4.32] mg/l, Css 4.73 [2.91; 6.70] mg/l. Statistically significant differences in CDR parameter between groups with LTG monotherapy and duotherapy, both with inducer and with inhibitors, as well as between groups of duotherapy with inductors and with inhibitors were obtained. The results of the study indicate a pronounced pharmacokinetic variability of the LTG. Conducting TDM allows the establishment of individual therapeutic concentrations of LTG in blood plasma and setting a correction vector for antiepileptic therapy.
评估拉莫三嗪（LTG）的药代动力学变异性及其临床意义。
对100例年龄在18至77岁（38.23±14.37岁）的局灶性癫痫患者进行检查，其中包括74名女性。54例患者接受LTG单药治疗，46例患者接受联合治疗（27例患者使用LTG与丙戊酸联合治疗，19例患者使用LTG与肝酶诱导剂联合治疗）。患者接受了治疗药物监测（TDM）程序。计算了LTG血浆稳态最小浓度（Css）和最大浓度（Css）以及浓度与体重比（CDR）。
在接受LTG单药治疗的患者中，LTG的Css为5.6±4.65mg/l，Css为7.59±5.54mg/l。在接受LTG与丙戊酸盐联合治疗的组中，LTG的Css为7.8[5.4；11.8]mg/l，Css为11.4[7.3；15.3]mg/l。在接受LTG与葡萄糖醛酸化药物诱导剂联合治疗的组中，Css为2.5[1.99；4.32]mg/l，Css为4.73[2.91；6.70]mg/l。LTG单药治疗组与联合治疗组（包括与诱导剂和抑制剂联合治疗）之间以及联合治疗的诱导剂组与抑制剂组之间的CDR参数存在统计学显著差异。研究结果表明LTG具有明显的药代动力学变异性。进行TDM可以确定血浆中LTG的个体治疗浓度，并为抗癫痫治疗设定校正指标。
