Eriksson A S, Boreus L O
Department of Pediatrics, Karolinska Hospital, Stockholm, Sweden.
Ther Drug Monit. 1997 Oct;19(5):499-501. doi: 10.1097/00007691-199710000-00002.
It has been suggested that lamotrigine (LTG) may enhance the toxicity of carbamazepine (CBZ) by increasing the concentration of the active metabolite carbamazepine-10,11-epoxide (CBZ-E) in adult patients. The authors investigated this hypothesis in an add-on study in 11 children and 3 adolescents, aged 6-22 years, who had been treated for more than 1 year with CBZ in monotherapy or with CBZ in combination with one or two other antiepileptic drugs. The LTG dosage was increased step by step until clinical response or side effects were observed. The plasma concentrations of LTG, CBZ, and CBZ-E were monitored during steady state conditions before and after the addition of LTG. It was found that LTG had no effect on mean CBZ concentrations and that it decreased rather than increased the mean plasma concentration of CBZ-E from 6.4 +/- 2.6 to 4.9 +/- 2.4 mumol/l (mean +/- SD, n = 14, P = 0.019). Observed side effects were diplopia in two children, agitation in two, and increased number of seizures in one. None of these five patients had unusually high CBZ-E levels when the side effect developed. It is concluded that addition of lamotrigine in children treated with carbamazepine children does not result in a pharmacokinetic interaction with a toxic accumulation of carbamazepine-10,11-epoxide.
有人提出，拉莫三嗪（LTG）可能通过提高成年患者体内活性代谢物卡马西平-10,11-环氧化物（CBZ-E）的浓度来增强卡马西平（CBZ）的毒性。作者在一项附加研究中对11名儿童和3名青少年（年龄6 - 22岁）进行了调查，这些儿童和青少年接受CBZ单药治疗或CBZ与一种或两种其他抗癫痫药物联合治疗超过1年。逐步增加LTG剂量，直至观察到临床反应或副作用。在添加LTG之前和之后的稳态条件下监测LTG、CBZ和CBZ-E的血浆浓度。结果发现，LTG对CBZ的平均浓度没有影响，并且它使CBZ-E的平均血浆浓度从6.4±2.6降至4.9±2.4μmol/l（平均值±标准差，n = 14，P = 0.019），即不是升高而是降低了其浓度。观察到的副作用包括两名儿童出现复视，两名儿童出现激动，一名儿童癫痫发作次数增加。在出现副作用时，这五名患者中没有一人的CBZ-E水平异常高。得出的结论是，在接受卡马西平治疗的儿童中添加拉莫三嗪不会导致与卡马西平-10,11-环氧化物的毒性蓄积发生药代动力学相互作用。
