Gidal B E, Anderson G D, Rutecki P R, Shaw R, Lanning A
Department of Neurology, School of Pharmacy, University of Wisconsin, Madison, WI, USA.
Epilepsy Res. 2000 Nov;42(1):23-31. doi: 10.1016/s0920-1211(00)00160-1.
to describe the population pharmacokinetics of lamotrigine (LTG) in developmentally disabled (DD) patients with epilepsy and (2) to determine if there is an effect of valproate (VPA) concentration on the extent of the pharmacokinetic interaction between VPA and LTG.
a NONMEM population analysis of steady-state LTG serum concentrations was conducted in patients receiving LTG either as mono or polytherapy with either an enzyme inducer (IND)-carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB) or an inhibitor (VPA).
sixty-two patients (33.6+/-11.3 years, 47+/-9.9 kg) receiving LTG monotherapy (n=19) or polytherapy with VPA (n=15), inducer(s) (n=32) or both (n=5) were evaluated. LTG dose of 369+/-236 mg per day (8.1+/-5.9 mg/kg per day) achieved LTG plasma concentrations of 6.8+/-3.3 microg/ml. The observed LTG monotherapy, LTG+IND, and LTG+VPA oral clearance (Cl/F) were 0. 69+/-0.2, 1.60+/-0.65 and 0.2+/-0.05 ml/kg per min, respectively. The final LTG Cl/F model was dependent on body weight, concomitant VPA, and either single or multiple inducers. Including the serum concentrations of CBZ, PHT, or VPA in the model, did not significantly improve estimates of Cl/F.
LTG Cl/F in DD patients is similar to literature values for ambulatory adult patients; however, low weight adult patients have higher elimination rates, as well as an increased response to enzyme induction. VPA inhibition of LTG Cl/F is maximal within the usually accepted therapeutic range for VPA.
（1）描述拉莫三嗪（LTG）在发育障碍（DD）癫痫患者中的群体药代动力学，（2）确定丙戊酸盐（VPA）浓度对VPA与LTG之间药代动力学相互作用程度是否有影响。
对接受LTG单药治疗或与酶诱导剂（IND）——卡马西平（CBZ）、苯妥英（PHT）、苯巴比妥（PB）联合用药或与抑制剂（VPA）联合用药的患者进行非房室群体分析，分析稳态LTG血清浓度。
评估了62例接受LTG单药治疗（n = 19）或与VPA联合用药（n = 15）、诱导剂联合用药（n = 32）或两者联合用药（n = 5）的患者（33.6±11.3岁，47±9.9 kg）。每日369±236 mg（8.1±5.9 mg/kg）的LTG剂量使LTG血浆浓度达到6.8±3.3 μg/ml。观察到的LTG单药治疗、LTG + IND和LTG + VPA的口服清除率（Cl/F）分别为0.69±0.2、1.60±0.65和0.2±0.05 ml/kg每分钟。最终的LTG Cl/F模型取决于体重、同时使用的VPA以及单一或多种诱导剂。在模型中纳入CBZ、PHT或VPA的血清浓度，并未显著改善Cl/F的估计值。
DD患者中LTG的Cl/F与门诊成年患者的文献值相似；然而，低体重成年患者的消除率更高，对酶诱导的反应也增强。VPA对LTG Cl/F的抑制在VPA通常认可的治疗范围内最大。
