Does Carbamazepine-Epoxide Conjugate with Glutathione? On an Existing but Almost Forgotten Possibility

Kalapos, Miklös Péter; Debreczeni, J.; Széll, Krisztián; Olajos, S; Herczeg, I

doi:10.1515/dmdi.2000.16.3.229

Drug Metabolism and Drug Interactions

2000

DOI: 10.1515/dmdi.2000.16.3.229

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Does Carbamazepine-Epoxide Conjugate with Glutathione? On an Existing but Almost Forgotten Possibility

Miklös Péter Kalapos¹,

J. Debreczeni²,

Krisztián Széll³

et al.

Abstract: The anticonvulsant carbamazepine is widely used to treat affective disorders and behavioural disorders in non-epileptic children. We report an elevated plasma level of carbamazepine-10,11-epoxide in a cystinuric child after daily medication with 300 mg carbamazepine while the serum level of carbamazepine was in the therapeutic range. The concentrations of carbamazepine and its epoxide derivative were determined by HPLC. The formation of a glutathione conjugate of carbamazepine-10,11-epoxide is raised as a hypo… Show more

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2002

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Carbamazepine-Provoked Hepatotoxicity and Possible Aetiopathological Role of Glutathione in the Events

Kalapos¹

2002

Adv Drug React Toxicol Rev

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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 carbamazepine hepatotoxicity is rare, and unpredictable with the present state of knowledge, but it is somehow related to disturbance of glutathione metabolism, although data in this regard are imperfect. There appear to be two types of carbamazepine-initiated idiosyncratic liver injury, hypersensitivity and toxin-induced. It is feasible that both are due to the accumulation of toxic metabolite(s), and arene oxides may probably be considered as damaging derivatives of carbamazepine metabolism. Despite the lack of clear-cut underlying clinical and experimental findings in those patients in whom an inherited weakness of drug eliminating capacity is present, those conditions that may deteriorate glutathione balance, may increase the possibility of the emergence of toxic events during carbamazepine therapy. Finally, some recommendations for carbamazepine therapy are presented.

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Carbamazepine-Provoked Hepatotoxicity and Possible Aetiopathological Role of Glutathione in the Events

Kalapos¹

2002

Adv Drug React Toxicol Rev

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Does Carbamazepine-Epoxide Conjugate with Glutathione? On an Existing but Almost Forgotten Possibility

Cited by 1 publication

References 12 publications

Carbamazepine-Provoked Hepatotoxicity and Possible Aetiopathological Role of Glutathione in the Events

Carbamazepine-Provoked Hepatotoxicity and Possible Aetiopathological Role of Glutathione in the Events

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