Carbamazepine-Provoked Hepatotoxicity and Possible Aetiopathological Role of Glutathione in the Events
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Adv Drug React Toxicol Rev 2002; 21 (3): 123-141 0964-198X/02/0003-0123/$25.00/0 © Adis International Limited. All rights reserved.
Carbamazepine-Provoked Hepatotoxicity and Possible Aetiopathological Role of Glutathione in the Events Retrospective Review of Old Data and Call for New Investigation Miklós Péter Kalapos Theoretical Biology Research Group, Budapest, Hungary
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Indication Categories and Adverse Effects of Carbamazepine . . . . . . . . . . . . . . . 1.1 Clinical Application of Carbamazepine . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Epidemiology of the Adverse Effects of Carbamazepine . . . . . . . . . . . . . . . . 2. Description of Carbamazepine Metabolism and Toxicity . . . . . . . . . . . . . . . . . . . 2.1 Main Routes of Carbamazepine Metabolism . . . . . . . . . . . . . . . . . . . . . . . 2.2 Interrelationship between Glutathione and Carbamazepine Metabolism . . . . . . 2.2.1 Experimental Data from Laboratory Animals and Human Tissues . . . . . . . . 2.2.2 Clinical Data on the Glutathione-Dependent Metabolism of Carbamazepine 2.2.3 In Vitro Studies with Clinical Relevance . . . . . . . . . . . . . . . . . . . . . . . 3. Carbamazepine-Induced Hepatotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Method for the Evaluation of Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Reversible Liver Abnormalities during Carbamazepine Therapy . . . . . . . . . . . . 3.3 Hepatic Deaths Related to Carbamazepine Therapy . . . . . . . . . . . . . . . . . . 3.4 Effects of Carbamazepine Overdosage on Liver Function . . . . . . . . . . . . . . . 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Descriptive Summary of Retrospective Data Analysis . . . . . . . . . . . . . . . . . . 4.2 Classification and Possible Mechanisms of Carbamazepine-Induced Hepatotoxicity . . 5. Conclusions and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Abstract
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The antiepileptic drug (AED) carbamazepine is widely used in the treatment of different kinds of seizures as well as affective and behavioural disorders. This paper presents an epidemiological study of carbamazepine-induced hepatic injuries and death, and describes the possible mechanisms of its toxicity. A retrospective analysis of clinical data revealed that the likelihood of hepatic death was comparatively higher in children, particularly when they were receiving medication with multiple AEDs, whereas reversible hepatic injuries were more likely to be seen in elderly patients. As suggested in this paper, the development of carba-
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