Winnicka Renata I, Topaciński Bogdan, Szymczak Wiesław M, Szymańska Bozena
Department of Chemical and Dust Hazards, Nofer Institute of Occupational Medicine, Lodz, Poland.
J Toxicol Clin Toxicol. 2002;40(6):759-65. doi: 10.1081/clt-120015836.
Carbamazepine (amizepine) is a widely used psychotropic agent. A much easier accessibility of this drug, observed during the recent years, may account for an increasing number of acute intoxications with carbamazepine. The aim of this study was to determine the elimination kinetics of carbamazepine and its metabolite carbamazepine 10,11-epoxide, and to identify the quantitative relationship between concentrations of these compounds, in serum. The subjects were 41 patients with acute carbamazepine intoxication. Serum carbamazepine and carbamazepine 10,11-epoxide concentrations were determined every 6 hours during thefirst 24 hours of hospitalization, and then every 12 hours. At the same time, urinalyses were performed for each patient to confirm or exclude homogeneity of poisoning. Depending on the type of intoxication (homogenous or combined), three groups of patients, and on the method of treatment (symptomatic, charcoal administration), two groups of patients were distinguished. The statistical analysis of the results revealed that among the investigated parameters (time-integrated concentrations of carbamazepine and carbamazepine 10,11-epoxide in serum, the presence of drugs, and/or ethanol, charcoal treatment) only carbamazepine concentrations had statistically significant effect on the duration of coma regarded as a critical effect. The kinetics of carbamazepine elimination was determined on the basis of the mean carbamazepine concentrations at the same timing of sampling for each patient in all the three groups; the mean carbamazepine elimination in serum followed zero-order kinetics. In individual groups, the decrease in serum carbamazepine concentrations ranged from 0.5 to 0.8 mg L(-1) hour(-1). Contrary to the suggestions found in the literature, carbamazepine 10,11-epoxide determination does not seem to enhance the possibility of anticipating the course of intoxication or the time of recovery.
卡马西平（酰胺咪嗪）是一种广泛使用的精神药物。近年来观察到这种药物的可及性大大提高，这可能是卡马西平急性中毒病例增多的原因。本研究的目的是确定卡马西平和其代谢物卡马西平10,11 - 环氧化物的消除动力学，并确定这些化合物在血清中的浓度之间的定量关系。研究对象为41例急性卡马西平中毒患者。在住院的前24小时内每6小时测定一次血清卡马西平和卡马西平10,11 - 环氧化物的浓度，之后每12小时测定一次。同时，对每位患者进行尿液分析以确认或排除中毒的同质性。根据中毒类型（同质或混合）将患者分为三组，根据治疗方法（对症治疗、给予活性炭）将患者分为两组。结果的统计分析表明，在所研究的参数（血清中卡马西平和卡马西平10,11 - 环氧化物的时间积分浓度、药物和/或乙醇的存在、活性炭治疗）中，只有卡马西平浓度对被视为关键效应的昏迷持续时间有统计学显著影响。基于三组中每位患者在相同采样时间的平均卡马西平浓度确定了卡马西平的消除动力学；血清中卡马西平的平均消除遵循零级动力学。在各个组中，血清卡马西平浓度的下降范围为0.5至0.8 mg L⁻¹小时⁻¹。与文献中的建议相反，测定卡马西平10,11 - 环氧化物似乎并不能增加预测中毒过程或恢复时间的可能性。
