Comment

Abstract

As described in these case vignettes, any strategy for the drug treatment of epilepsy in a patient with AIDS, asthma, or stroke needs to take into account the clinical importance of the P450 cytochromes (CYP) and the potential impact that antiepileptic drugs (AEDs) may have on the disease process. The human CYP superfamily comprises 57 genes. These genes code for enzymes that can have, among a host of other functions, a role in the metabolism of AEDs and vitamin D synthesis and metabolism [ [1] Nebert D.W. Russell D.W. Clinical importance of the cytochromes P450. Lancet. 2002; 360: 1155-1162 Abstract Full Text Full Text PDF PubMed Scopus (1087) Google Scholar ]. For our cases, these two aspects are particularly relevant. Hepatic concentrations of human CYP enzymes are increased by consumption of many of the drugs that are prescribed for epilepsy. This induction leads to enhanced clearance of other drugs that are also CYP substrates. The ability of one CYP substrate to affect the concentration of another in this manner is the basis for so-called drug–drug interactions, which complicate treatment as seen in our cases. In addition, AEDs may also inhibit CYP enzymes; for example, valproate is a broad enzyme inhibitor and affects many drug clearance pathways, while phenytoin, carbamazepine, phenobarbital, and primidone are broad examples of enzyme inducers. Such inhibitory drug–drug interactions are even more disturbing as they may lead to decreased clearance with ensuing toxicity due to increasing serum concentrations of AEDs given in combination.