Carbamazepine poisoning: elimination kinetics and quantitative relationship with carbamazepine 10,11-epoxide.

Abstract

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.