[Antiepileptic drugs and the liver]

We review the metabolism of antiepileptic drugs with particular emphasis on the formation of active metabolites and toxic intermediate metabolites, together with the factors altering this and the possibility of interactions between the antiepileptic drugs themselves and with other drugs.

Most antiepileptic drugs undergo complex metabolic processes in the liver which determine the time course of their concentration in the organism and therefore their therapeutic and toxic effects. Also, the processes by which drugs are metabolised may be influenced by many physiological and pathological factors, as well as the presence of other drugs which cause clinically relevant interactions. We analyze the function of the liver in the metabolism of these drugs with special reference to the microsome oxidation mediated by cytochrome P-450 and the glucuronidation catalysed by glucuronosyltransferase and the processes of enzyme induction and inhibition. Subsequently, we describe the metabolism of the antiepileptic drugs, their main routes of elimination, factors affecting this, role of the active and intermediate metabolites and the involvement of the enzyme induction and inhibition underlying the interactions of these drugs. Finally, we describe the metabolism of the most important classical and new antiepileptic drugs, the isoforms of cytochrome P-450 involved, the factors altering this and the most relevant interactions with other antiepileptic and non-antiepileptic drugs.

Knowledge of the paths by which the antiepileptic drugs are metabolised, particularly the isoforms of cytochrome P-450 involved facilitates understanding of the influence of various factors on the metabolism of drugs, and also of their complex interactions.