Pharmacogenomics and adverse drug reactions in children

Abstract

Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children.

Keywords: adverse drug reactions; childhood cancer; children; ethics of research in children; pharmacogenomics.

Figure 1

Metabolism of 6-Mercaptopurine (6-MP). Metabolism of 6-MP via Hypoxanthine-guanine Phosphoribosyltransferase produces active Thioguanine nucleotide analogues while metabolism of 6-MP by Thiopurine Methyltransferase produces inactive 6-methylmercaptopurine. Genetically determined variations in 6-MP metabolism can produce significant differences in efficacy and safety.