Idiosyncratic drug reactions: interaction of development and genetics

There is a major need for biologic markers closely linked to the mechanisms of susceptibility and toxicity of xenobiotics that can aid in elucidation of populations at risk. Such markers, genetic or developmental, need to be interpreted in light of the mechanism of toxicity of the specific compound. It is likely that maximum progress in this area will be made by integration of biologic markers of susceptibility (closely linked to the basic toxicologic mechanisms of the compound in question) with human epidemiologic studies. "New" pharmacogenetic variants in drug metabolism are being discovered at an ever-increasing rate. Molecular biology approaches to variant genes, as well as in vivo and cellular probes of toxicologically important metabolic pathways, are likely to serve as significant tools in predicting who is at risk for an ADR, and in confirming clinical impressions of ADR causality. Linked with epidemiologic studies of ADR incidence, it will be increasingly possible to discover the relative roles of development and genetics in ADRs.