Oxcarbazepine (OXCBZ), a second-generation anticonvulsant used in the long-term treatment of epilepsy, was added to the set of treatment choices with the aim to overcome the most common adverse effects of carbamazepine (CBZ), a widely used first-generation antiepileptic. However, while eliciting milder symptoms, OXCBZ is associated with the same adverse reactions induced by CBZ.<br/>Currently, little is known about the mechanisms underlying OXCBZ-induced toxic outcomes; nonetheless, drug bioactivation is anticipated to be a major cause of these events. This assumption led us to investigate the biologically plausible Phase II sulfonation of the reduced monohydroxy derivative (licarbazepine, MHD), which is the clinically relevant OXCBZ metabolite. Interestingly, all attempts to obtain the sulfonation product of MHD, either by standard chemical methods or under biologically relevant conditions, led to the formation of CBZ, stemming from an elimination process. CBZ formation, following MHD sulfonation, is consistent with the previously reported identification of CBZ in the plasma of patients on OXCBZ therapy, and represents a credible explanation for the similar but milder/delayed adverse reactions associated with OXCBZ as compared to CBZ.<br/>         <br/>

Adverse reactions induced by the antiepileptic drug oxcarbazepine may stem from its metabolic biotransformation to carbamazepine

256th National Meeting (2018)

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