Leach J P, Blacklaw J, Jamieson V, Jones T, Richens A, Brodie M J
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Epilepsia. 1996 Nov;37(11):1100-6. doi: 10.1111/j.1528-1157.1996.tb01031.x.
We wished to determine mutual interaction of two drugs with active metabolism: remacemide, hydrochloride and carbamazepine (CBZ).
A randomized, double-blind, placebo-controlled cross-over study of add-on remacemide hydrochloride was performed in 10 of 14 recruited patients being treated with CBZ monotherapy. Forty-eight-hour concentration profiles of CBZ, its active epoxide metabolite (CBZ-E), remacemide, and its desglycinyl metabolite (ARL12495XX) were assayed after single and multiple dosing.
After patients were treated with 300 mg remacemide hydrochloride twice daily for 14 days, the mean area under the concentration-time curve (AUC) of CBZ was increased by 22% (p = 0.12), Cmax was increased by 27% (p = 0.07), and Cmin was increased by 22% (p = 0.29). Trough concentrations of CBZ were higher (p = 0.0037) during active treatment as compared with placebo treatment. CBZ-E levels were unaffected. No symptoms of CBZ toxicity were reported. There was no evidence of autoinduction of remacemide metabolism. However, in CBZ-treated patients, the AUC of remacemide and its active metabolite was 60 and 30%, respectively, of values observed in healthy volunteers treated previously with the same dose.
Remacemide hydrochloride inhibits CBZ metabolism, which itself induces that of remacemide hydrochloride and its active metabolite. This mutual interaction between remacemide hydrochloride and CBZ is predictable and modest and should not present a barrier to their clinical use in combination.
我们希望确定两种具有活性代谢的药物——盐酸瑞马西胺和卡马西平（CBZ）之间的相互作用。
对14名接受CBZ单药治疗的招募患者中的10名进行了一项随机、双盲、安慰剂对照的盐酸瑞马西胺附加治疗交叉研究。在单次和多次给药后，测定了CBZ及其活性环氧化物代谢物（CBZ-E）、瑞马西胺及其去甘氨酰代谢物（ARL12495XX）的48小时浓度曲线。
患者每日两次服用300 mg盐酸瑞马西胺，持续14天后，CBZ的浓度-时间曲线下面积（AUC）平均增加22%（p = 0.12），Cmax增加27%（p = 0.07），Cmin增加22%（p = 0.29）。与安慰剂治疗相比，活性治疗期间CBZ的谷浓度更高（p = 0.0037）。CBZ-E水平未受影响。未报告CBZ毒性症状。没有证据表明瑞马西胺代谢存在自身诱导作用。然而，在接受CBZ治疗的患者中，瑞马西胺及其活性代谢物的AUC分别为先前接受相同剂量治疗的健康志愿者所观察值的60%和30%。
盐酸瑞马西胺抑制CBZ代谢，而CBZ本身诱导盐酸瑞马西胺及其活性代谢物的代谢。盐酸瑞马西胺与CBZ之间的这种相互作用是可预测的且程度适中，不应成为它们联合临床应用的障碍。
