Some aspects of interindividual variations in the metabolism of xenobiotics

Abstract

Differences in drug metabolism among individuals are caused by numerous factors: differences in production and stability of mRNA of xenobiotic metabolizing enzymes, differences in the rate of enzyme synthesis and degradation, or enzyme inhibition. One of the most important reasons is genetic polymorphism of cytochrome P450 genes or cyto-chrome P450 regulatory factors. Nuclear receptors play great role in the regulation of these genes. The presence of the ligand induces the nuclear receptor to bind to the dimerisation partner and as a hetero/homodimer it can activate the DNA responsive element. In addition, several co-activators, co-repressors and other factors can modulate the effect of nuclear receptors. Hepatic levels of cytochrome P450 enzymes are reduced in multiple models of inflammation or infection.

Cytochrome P450 enzymes of four families (CYP1-CYP4) are known to be involved in xenobiotic metabolism. Their genetic polymorphism and regulation are discussed in this review.